Methods of protecting an organ using tetrahydrocurcumin and phosphatidylcholine

ABSTRACT

Pharmaceutical formulations of tetrahydrocurcumin and liposomes are described herein. The liposomes may comprise at least a first lipid, wherein the first lipid is a phospholipid or polyenylphosphatidylocholine are also disclosed.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication are hereby incorporated by reference under 37 CFR 1.57, forexample, the present application is a continuation of U.S. applicationSer. No. 15/190,689, filed Jun. 23, 2016, which is a continuation ofU.S. application Ser. No. 14/841,229, filed Aug. 31, 2015, now U.S. Pat.No. 9,375,408, issued Jun. 28, 2016, which claims the benefit ofpriority to U.S. Provisional Application No. 62/044,566, filed Sep. 2,2014, the disclosure of each of which is hereby incorporated byreference in its entirety.

BACKGROUND

Many drugs can be administered through the oral route as liquids,capsules or tablets. As oral administration is a safe, convenient andcost effective route, it is the route taken for most therapeutics.However oral administration has several limitations. Orally administereddrugs bypass the mouth and the stomach in order to be absorbed into thesystem for use. Drug absorption can begin in the mouth and stomach, andcan be finally absorbed by the small intestine, passing the intestinalwalls, passing through the liver for processing, and then finally betransported through the bloodstream to reach its target site. As such,the drugs can be metabolized before the blood and plasma are reached.

Drugs can be metabolized by oxidation, reduction, hydrolysis,conjugation, condensation and other additional processes that can makethe drug easier for a subject to excrete. Some drugs can be metabolizedso rapidly that a therapeutically effective concentration in the bloodis not reached.

A property of orally administered drugs that can affect its ability toreach its destined tissue or site of treatment can be its absorption andsolubility. Solubility behavior is a challenge for many drugs, which canrequire pharmaceutical formulations with solubility enhancers in orderto improve its ability to become absorbed by a system for use.Solubility is a phenomenon of dissolution of solute into a solvent togive a homogenous system and is important for achieving a desiredconcentration of drug in a systemic circulation for a desiredpharmacological response. The solubility of a drug is intrinsicallyrelated to its size and its properties. Low aqueous solubility is aproblem for many drugs, as a drug will need to be in a form of asolution at the site of absorption, such as within the gastro-intestinaltract. To date, more than 40% of chemical entities developed for thepharmaceutical industry are poorly soluble in water. Solubility howevercan be increased by the drug solutions of oil in water emulsion,addition of a hydrophilic carrier, cellulosic derivatives, lipids,phospholipids and antioxidants. As such, methods are needed to increasethe bioavailability of a drug, such as methods to slow the metabolism ofa drug and increase solubility of a drug, in a subject in need isneeded.

SUMMARY

In one aspect, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. The method includes, for example,administering a pharmaceutical formulation to the subject. Thepharmaceutical formulation may include a non-deuterated form oftetrahydrocurcumin or a deuterated form of tetrahydrocurcumin and apharmaceutical vehicle. In some embodiments, the disorder is selectedfrom a group including fatty liver disease, alcoholic liver disease,kidney disease, diabetic kidney disease, polycystic kidney disease,hypertension, hypertension with left ventricular hypertrophy, heartfailure, diabetes and diabetes with hyperlipidemia. In some embodiments,the subject has elevated levels of Galectin-3, fibrotic markers, markersof oxidative stress, and/or markers of inflammation in the blood and/orurine. In some embodiments, the subject is taking analgesics. In someembodiments, the subject is under treatment with one or moreanti-malarial drugs. In some embodiments, the pharmaceutical formulationis administered by oral administration or intravenous administration.

In another aspect, a method of protecting an organ is provided. Themethod includes, for example, identifying a subject in need ofprotection of an organ and administering a pharmaceutical formulation toa subject in need thereof, the pharmaceutical formulation including anon-deuterated form of tetrahydrocurcumin or a deuterated form oftetrahydrocurcumin and a pharmaceutical vehicle. In some embodiments,the organ is selected from a group including kidney, liver and heart. Insome embodiments, the administering is performed by oral administrationor intravenous administration. In some embodiments, the subject has adisorder selected from a group including liver disorder, fatty liverdisease, alcoholic liver disease, kidney disease, diabetic kidneydisease, polycystic kidney disease, hypertension, hypertension with leftventricular hypertrophy, diabetes, diabetes with hyperlipidemia andheart failure. In some embodiments, the subject has an elevated level ofGalectin-3, fibrotic markers, markers of oxidative stress and/or one ormore markers of inflammation in the blood and/or urine.

In another aspect a method of treating or preventing heart failure in asubject in need thereof is provided. The method includes, for example,identifying a subject in need of treatment for or prevention of heartfailure and administering pharmaceutical formulation to a subject inneed thereof, the pharmaceutical formulation including a non-deuteratedform of tetrahydrocurcumin or a deuterated form of tetrahydrocurcuminand a pharmaceutical vehicle. In some embodiments, the subject haschronic kidney disease and/or hypertension. In some embodiments, theadministering is oral administration or intravenous administration.

In another aspect a pharmaceutical formulation includes a non-deuteratedform of tetrahydrocurcumin or a deuterated form of tetrahydrocurcuminand a pharmaceutical vehicle is provided. In some embodiments, thepharmaceutical formulation includes, for example, a first lipid. In someembodiments, the first lipid is a phospholipid orpolyenylphosphatidylcholine. In some embodiments, the pharmaceuticalformulation includes at least 5% of the first lipid by weight and nomore than 95% of the first lipid by weight. In some embodiments, thepharmaceutical formulation further includes a second lipid. In someembodiments, the pharmaceutical formulation includes at least 5% of thesecond lipid by weight and no more than 95% of the second lipid byweight. In some embodiments, the pharmaceutical formulation furtherincludes an antioxidant. In some embodiments, the pharmaceuticalformulation includes at least 5% of antioxidant by weight and no morethan 95% of the antioxidant by weight. In some embodiments, theantioxidant is selected from a group consisting of Vitamin E, Vitamin Cand alpha lipoic acid. In some embodiments, the pharmaceuticalformulation further includes curcumin, a terpenoid, cysteamine,pantethine, and/or baicalin. In some embodiments, the vehicle is alipophilic solvent, fatty oil, organic oil, or liposome. In someembodiments, the pharmaceutical formulation further includes anexcipient. In some embodiments, the excipient is a sugar, lactose,sucrose, mannitol, sorbitol, cellulose preparations of maize starch,wheat starch, rice starch, potato starch, gelatin, gum tragacanth,methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP).

In a first aspect, a method treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the methodincludes administering the pharmaceutical formulation including anon-deuterated form of tetrahydrocurcumin of any of the embodimentsdescribed herein. In some embodiments, the disorder is a liver disorder.In some embodiments, the disorder is a fatty liver disease. In someembodiments, the disorder is alcoholic liver disease. In someembodiments, the disorder is a kidney disease. In some embodiments, thedisorder is diabetic kidney disease. In some embodiments, the disorderis polycystic kidney disease. In some embodiments, the disorder ishypertension. In some embodiments, the disorder is hypertension withleft ventricular hypertrophy. In some embodiments, the disorder isdiabetes. In some embodiments, the disorder is diabetes withhyperlipidemia. In some embodiments, the subject has elevated Galectin-3levels in the blood and/or urine. In some embodiments, the subject haselevated levels of fibrotic markers. In some embodiments, the fibroticmarkers are in blood. In some embodiments, the fibrotic markers are inurine. In some embodiments, the subject has an elevated level of amarker of oxidative stress. In some embodiments, the marker of oxidativestress is in blood. In some embodiments, the marker of oxidative stressis in urine. In some embodiments, the subject has an elevated level of amarker of inflammation. In some embodiments, the marker of inflammationis in blood. In some embodiments, the marker of inflammation is inurine. In some embodiments, the pharmaceutical formulation isadministered to the subject by oral administration. In some embodiments,the administering is performed by intravenous administration. In someembodiments, the subject is human. In some embodiments, the subject istaking analgesics. In some embodiments, the subject is under treatmentwith one or more anti-malarial drugs. In some embodiments, the subjecthas heart failure.

In a second aspect, a method of protecting an organ is provided. In someembodiments, the method includes identifying a subject in need ofprotection of an organ; and administering the pharmaceutical formulationincluding a non-deuterated form of tetrahydrocurcumin of any of theembodiments described herein to a subject in need. In some embodiments,the method includes identifying a subject in need of protection of anorgan and administering the pharmaceutical formulation including anon-deuterated form of tetrahydrocurcumin according to any of theembodiments described herein to the subject in need. In someembodiments, the organ is kidney. In some embodiments, the organ isliver. In some embodiments, the subject is human. In some embodiments,the organ is heart.

In some embodiments, the administering is performed by oraladministration. In some embodiments, the administering is performed byintravenous administration. In some embodiments, the subject has a liverdisorder. In some embodiments, the subject has a fatty liver disease. Insome embodiments, the subject has alcoholic liver disease. In someembodiments, the subject has a kidney disease. In some embodiments, thesubject has diabetic kidney disease. In some embodiments, the subjecthas polycystic kidney disease. In some embodiments, the subject hasheart failure.

In some embodiments, the subject has hypertension. In some embodiments,the subject has hypertension with left ventricular hypertrophy. In someembodiments, the subject has diabetes. In some embodiments, the subjecthas diabetes with hyperlipidemia.

In some embodiments, the subject has an elevated level of Galectin-3 inthe blood. In some embodiments, the subject has an elevated level of oneor more fibrotic markers. In some embodiments, the one or more fibroticmarkers are in blood. In some embodiments, at least one of the one ormore fibrotic markers is in urine. In some embodiments, the subject hasan elevated level of one or more markers of oxidative stress. In someembodiments, at least one of the markers of oxidative stress is inblood. In some embodiments, at least one of the markers of oxidativestress is in urine. In some embodiments, the subject has an elevatedlevel of one or more markers of inflammation. In some embodiments, atleast one of the elevated markers of inflammation is in blood. In someembodiments, at least one of the elevated markers is in urine.

In a third aspect, a method of treatment or preventing heart failure ina subject in need is provided. The method can include identifying asubject in need of treatment for or prevention of heart failure andadministering the pharmaceutical formulation including a non-deuteratedform of tetrahydrocurcumin of any one of the embodiments describedherein to a subject in need. In some embodiments, the subject haschronic kidney disease and/or hypertension. In some embodiments, thesubject is human. In some embodiments, the administering is performed byoral administration. In some embodiments, the administering is performedby intravenous administration.

In a fourth aspect, a pharmaceutical formulation is provided. In someembodiments, the pharmaceutical formulation includes a non-deuteratedform of tetrahydrocurcumin and a pharmaceutical vehicle. In someembodiments, the pharmaceutical formulation includes a first lipid. Insome embodiments, the first lipid is a phospholipid. In someembodiments, the first lipid is polyenylphosphatidylcholine. In someembodiments, the pharmaceutical formulation includes at least 5% of thefirst lipid by weight. In some embodiments, the pharmaceuticalformulation includes no more than 95% of the first lipid by weight. Insome embodiments, the pharmaceutical formulation further includes asecond lipid. In some embodiments, the pharmaceutical formulationincludes at least 5% of the second lipid by weight. In some embodiments,the pharmaceutical formulation includes no more than 95% of the secondlipid by weight. In some embodiments, the second lipid is omega-3. Insome embodiments, the second lipid is omega-3 from fish or flaxseed. Insome embodiments, the pharmaceutical formulation includes anantioxidant. In some embodiments, the pharmaceutical formulationincludes at least 5% of antioxidant by weight. In some embodiments, thepharmaceutical formulation includes no more than 95% of the antioxidantby weight. In some embodiments, the antioxidant is Vitamin E. In someembodiments, the antioxidant is Vitamin C. In some embodiments, theantioxidant is alpha lipoic acid. In some embodiments, thepharmaceutical formulation further includes curcumin. In someembodiments, the pharmaceutical formulation further includes aterpenoid. In some embodiments, the pharmaceutical formulation furtherincludes cysteamine. In some embodiments, the pharmaceutical formulationfurther includes pantethine. In some embodiments, the curcumin isdeuterated. In some embodiments, the vehicle is a lipophilic solvent,fatty oil, organic oil, or liposome. In some embodiments, thepharmaceutical formulation further includes an excipient. In someembodiments, the excipient is a sugar, lactose, sucrose, mannitol,sorbitol, cellulose preparations of maize starch, wheat starch, ricestarch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP). In some embodiments, the pharmaceuticalformulation further includes baicalin.

In a fifth aspect, a non-deuterated form of tetrahydrocurcumin isprovided.

In a sixth aspect, a deuterated form of tetrahydrocurcumin is provided.In some embodiments, the deuterated form of tetrahydrocurcumin has nomore than fifteen deuterated sites. In some embodiments, the deuteratedform of tetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons.

In a seventh aspect, a method of making a deuterated form oftetrahydrocurcumin is provided. In some embodiments, the method includescontacting tetrahydrocurcumin in the presence of a catalyst anddeuterated water under a condition to form the deuterated form oftetrahydrocurcumin. In some embodiments, the method further includeshydrogenating curcumin to form the tetrahydrocurcumin. In someembodiments, the deuterated form of tetrahydrocurcumin has at least onedeuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than twenty-four deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons.

In some embodiments, the catalyst is palladium on carbon. In someembodiments, the catalyst is palladium barium carbonate. In someembodiments, the catalyst is palladium barium sulphate. In someembodiments, the catalyst is palladium silica. In some embodiments, thecatalyst is platinum on carbon. In some embodiments, the catalyst isplatinum-palladium carbon. In some embodiments, the catalyst is platinumalumina. In some embodiments, the catalyst is platinum calciumcarbonate. In some embodiments, the catalyst is platinum barium sulfate.In some embodiments, the catalyst is platinum silica. In someembodiments, the catalyst is platinum graphite.

In some embodiments, the method further includes purifying thedeuterated form of tetrahydrocurcumin. In some embodiments, thepurifying step includes isolating the deuterated form oftetrahydrocurcumin with column chromatography. In some embodiments, thedeuterated water is at least 25% deuterated. In some embodiments, thedeuterated water is at least 50% deuterated. In some embodiments, thedeuterated water is at least 75% deuterated. In some embodiments, thedeuterated water is 100% deuterated.

In an eighth aspect, a pharmaceutical formulation, for example apharmaceutical formulation, including a deuterated form oftetrahydrocurcumin is provided. In some embodiments, the pharmaceuticalformulation includes a deuterated form of tetrahydrocurcumin and apharmaceutical vehicle. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least onedeuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons.

In some embodiments, the pharmaceutical formulation further includes afirst lipid. In some embodiments, the first lipid is a phospholipid. Insome embodiments, the first lipid is polyenylphosphatidylcholine. Insome embodiments, the pharmaceutical formulation includes at least 5% ofthe first lipid by weight. In some embodiments, the pharmaceuticalformulation includes no more than 95% of the first lipid by weight. Insome embodiments, the pharmaceutical formulation includes a secondlipid. In some embodiments, the pharmaceutical formulation includes atleast 5% of the second lipid by weight. In some embodiments, thepharmaceutical formulation includes no more than 95% of the second lipidby weight. In some embodiments, the second lipid is omega-3. In someembodiments, the second lipid is omega-3 from fish or flaxseed.

In some embodiments, the pharmaceutical formulation includes anantioxidant. In some embodiments, the pharmaceutical formulationincludes at least 5% of antioxidant by weight. In some embodiments, thepharmaceutical formulation includes no more than 95% of the antioxidantby weight. In some embodiments, the antioxidant is Vitamin E. In someembodiments, the antioxidant is Vitamin C. In some embodiments, theantioxidant is alpha lipoic acid.

In some embodiments, the pharmaceutical formulation further includescurcumin. In some embodiments, the curcumin is deuterated. In someembodiments, the pharmaceutical formulation includes a terpenoid. Insome embodiments, the pharmaceutical formulation includes cysteamine. Insome embodiments, the pharmaceutical formulation includes pantethine. Insome embodiments, the pharmaceutical formulation includes baicalin. Insome embodiments, the vehicle is a lipophilic solvent, fatty oil,organic oil, or liposome. In some embodiments, the pharmaceuticalformulation further includes an excipient. In some embodiments, theexcipient is a sugar, lactose, sucrose, mannitol, sorbitol, cellulosepreparations of maize starch, wheat starch, rice starch, potato starch,gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP).

In a ninth aspect, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the methodincludes administering a pharmaceutical formulation includes adeuterated form of tetrahydrocurcumin according to any of theembodiments described herein to the subject. In some embodiments, thedisorder is a liver disorder. In some embodiments, the disorder is afatty liver disease. In some embodiments, the disorder is alcoholicliver disease. In some embodiments, the disorder is a kidney disease. Insome embodiments, the disorder is diabetic kidney disease. In someembodiments, the disorder is polycystic kidney disease.

In some embodiments, the disorder is hypertension. In some embodiments,the disorder is hypertension with left ventricular hypertrophy. In someembodiments, the disorder is diabetes. In some embodiments, the disorderis diabetes with hyperlipidemia. In some embodiments, the disorder isheart failure.

In some embodiments, the subject has elevated Galectin-3 levels in theblood. In some embodiments, the subject has elevated levels of fibroticmarkers. In some embodiments, the fibrotic markers are in blood. In someembodiments, the fibrotic markers are in urine. In some embodiments, thesubject has an elevated level of a marker of oxidative stress. In someembodiments, the marker of oxidative stress is in blood. In someembodiments, the marker of oxidative stress is in urine. In someembodiments, the subject has an elevated level of a marker ofinflammation. In some embodiments, the marker of inflammation is inblood. In some embodiments, the marker of inflammation is in urine.

In some embodiments, the pharmaceutical formulation is administered tothe subject by oral administration. In some embodiments, theadministering is performed by intravenous administration. In someembodiments, the subject is human. In some embodiments, theadministering is performed by intravenous administration. In someembodiments, the subject is under treatment with one or moreanti-malarial drugs.

In a tenth aspect a method of protecting an organ is provided. In someembodiments, the method includes identifying a subject in need ofprotection of an organ and administering the pharmaceutical formulationincluding a deuterated form of tetrahydrocurcumin according to any ofthe embodiments described herein to the subject in need. In someembodiments, the organ is kidney. In some embodiments, the organ isliver. In some embodiments, the organ is heart. In some embodiments, thesubject is human.

In some embodiments, the administering is performed by oraladministration. In some embodiments, the administering is performed byintravenous administration. In some embodiments, the subject has a liverdisorder. In some embodiments, the subject has a fatty liver disease. Insome embodiments, the subject has alcoholic liver disease. In someembodiments, the subject has a kidney disease. In some embodiments, thesubject has diabetic kidney disease. In some embodiments, the subjecthas polycystic kidney disease. In some embodiments, the subject hasheart failure.

In some embodiments, the subject has hypertension. In some embodiments,the subject has hypertension with left ventricular hypertrophy. In someembodiments, the subject has diabetes. In some embodiments, the subjecthas diabetes with hyperlipidemia.

In some embodiments, the subject has an elevated level of Galectin-3 inthe blood. In some embodiments, the subject has an elevated level of oneor more fibrotic markers. In some embodiments, the one or more fibroticmarkers are in blood. In some embodiments, at least one of the one ormore fibrotic markers is in urine. In some embodiments, the subject hasan elevated level of one or more markers of oxidative stress. In someembodiments, at least one of the markers of oxidative stress is inblood. In some embodiments, at least one of the markers of oxidativestress is in urine. In some embodiments, the subject has an elevatedlevel of one or more markers of inflammation. In some embodiments, atleast one of the elevated markers of inflammation is in blood. In someembodiments, at least one of the elevated markers is in urine.

In an eleventh aspect, a method of treating or treating or preventingheart failure in a subject in need is provided. In some embodiments, themethod includes identifying a subject in need of treatment for orprevention of heart failure administering the pharmaceutical formulationincluding a deuterated form of tetrahydrocurcumin of any one of any oneof the embodiments described herein to a subject in need. In someembodiments, the subject has chronic kidney disease and/or hypertension.In some embodiments, the subject is human. In some embodiments, theadministering is performed by oral administration. In some embodiments,the administering is performed by intravenous administration.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic illustration of tetrahydrocurcumin. Sites arenumbered on the schematic illustration of tetrahydrocurcumin to indicatenon-limiting exemplary deuteration sites. In one or more of thesedeuteration sites, there can be one, two, or three deuterons.

FIGS. 2A-2G show the measurements between the four groups of rats: 1)control rats 2) rats with chronic kidney disease (CKD), 3) rats treatedwith tetrahydrocurcumin after CDK, and 4) rats treated withtetrahydrocurcumin/curcumin after CDK. FIG. 2A shows the average bloodurea nitrogen (BUN) in the four groups of rats. FIG. 2B shows the changein BUN, or delta-BUN. FIG. 2C shows the Body Weight in the four groupsof rats FIG. 2D shows the amount of Hemoglobin (Hgb) in the four groupsof rats. FIG. 2E shows the Heart wt to Body wt (g/kg) ratio of the fourgroups of rats. FIG. 2F shows the systolic blood pressure in the fourgroups of rats. FIG. 2G shows the diastolic blood pressure in the fourgroups of rats.

DETAILED DESCRIPTION

Many drugs can be administered through the oral route as liquids,capsules or tablets. As oral administration is a safe, convenient andcost effective route, it is the route taken for most therapeutics.However oral administration has several limitations. Orally administereddrugs bypass the mouth and the stomach in order to be absorbed into thesystem for use. Drug absorption can begin in the mouth and stomach, andcan be finally absorbed by the small intestine, passing the intestinalwalls, passing through the liver for processing, and then finally betransported through the bloodstream to reach its target site. As such,the drugs can be metabolized before the blood and plasma are reached.

“Bioavailability” as described herein, refers to the absorption of adrug or drugs and is a subcategory of absorption as is the fraction ofan administered dose of unchanged drug that reaches the systemiccirculation and is one of the principal pharmacokinetic properties ofdrugs. Bioavailability thereby can refer to the extent and rate at whichthe active drug or metabolite enters the systemic circulation to reachthe site for action. Low bioavailability is the most common problem oforally administered drugs, as many are poorly water soluble and slowlyabsorbed drugs. The bioavailability of a drug is affected by thefunction of the intestinal walls and the liver, in which enzymaticreactions can metabolize the drug, thus decreasing the amount of thedrug that eventually reaches the blood stream for delivery. This ineffect decreases the bioavailability of a drug, or its extent and rateat which the active drug enters the systemic circulation.

Drugs can be metabolized by oxidation, reduction, hydrolysis,conjugation, condensation and other additional processes that can makethe drug easier for a subject to excrete. Some drugs can be metabolizedso rapidly that a therapeutically effective concentration in the bloodis not reached.

A property of orally administered drugs that can affect its ability toreach its destined tissue or site of treatment can be its absorption andsolubility. Solubility behavior is a challenge for many drugs, which canrequire pharmaceutical formulations with solubility enhancers in orderto improve its ability to become absorbed by a system for use.Solubility is a phenomenon of dissolution of solute into a solvent togive a homogenous system and is important for achieving a desiredconcentration of drug in a systemic circulation for a desiredpharmacological response. The solubility of a drug is intrinsicallyrelated to its size and its properties. Low aqueous solubility is aproblem for many drugs, as a drug will need to be in a form of asolution at the site of absorption, such as within the gastro-intestinaltract. To date, more than 40% of chemical entities developed for thepharmaceutical industry are poorly soluble in water. Solubility howevercan be increased by the drug solutions of oil in water emulsion,addition of a hydrophilic carrier, cellulosic derivatives, lipids,phospholipids and antioxidants. In some embodiments, a pharmaceuticalformulation is provided. In some embodiments, the pharmaceuticalformulation is administered to a subject by oral administration. In someembodiments, the subject is human. In some embodiments, theadministering is performed by intravenous administration.

Drug solutions of oil and surfactants can form oil in water emulsionsupon mixing with aqueous media in the gastro-intestinal tract, which canlead to an increase in drug absorption of a drug with poor solubility.Pharmaceutical formulations comprising lipids can also be used toincrease the bioavailability of a drug by increasing its absorption.Lipids, as described herein refers to fatty acids, or fatty acidresidues that are hydrophobic or amphiphilic small molecules that canform structures, liposomes, or membranes when exposed to an aqueousenvironment such as liquids in a gastro-intestinal tract. Lipids can becategorized into fatty acids, glycerolipids, glycerophospholipids,phospholipids, sphingolipids, sterol lipids, prenol lipids,saccharolipids, and polyketides. In some embodiments, a pharmaceuticalformulation comprising one or more lipids is provided. In someembodiments, the pharmaceutical formulation comprises a lipid. In someembodiments, the pharmaceutical formulation comprises a phospholipid.

Examples of phospholipids include, but are not limited to, phosphatidicacid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine,phosphatidylinositol, phosphatidylinositol phosphate,phosphatidylinositol bisphosphate, phosphatidylinositol triphosphate,ceramide phosphorylcholine, ceramide phosphorylethanolamine, ceramidephosphorylipid, phosphatidylcholine and polyenylphosphatidylcholine.Polyenylphosphatidyl choline can have the added benefit of increasingthe bioavailability by allowing absorption of a drug in the gut;additionally polyenylphosphatidyl choline has added benefits to hepatichealth. For example, polyenylphosphatidyl choline has been shown toreduce free phenol and ammonia concentrations in subjects suffering fromliver cirrhosis, this indicating that oxidative processes wereameliorated and detoxification processing in the liver was improved. Insome embodiments, the pharmaceutical formulation disclosed hereincomprises a non-deuterated form of tetrahydrocurcumin. In someembodiments, the pharmaceutical formulation comprises deuterated formsof tetrahydrocurcumin, as described in several embodiments herein. Insome embodiments, the pharmaceutical formulation disclosed hereincomprises a non-deuterated form of tetrahydrocurcumin and a deuteratedform of tetrahydrocurcumin, as described in several embodiments herein.In some embodiments, pharmaceutical formulations disclosed hereincomprise a lipid. In some embodiments, pharmaceutical formulationsdisclosed herein comprise a phospholipid. In some embodiments,pharmaceutical formulations disclosed herein comprisepolyenylphosphatidylcholine. In some embodiments, pharmaceuticalformulations disclosed herein comprise a phosphatidylcholine. Thepharmaceutical formulation disclosed herein can comprise a first lipid.The first lipid can be any of the lipids disclose herein or a mixturethereof. In some embodiments, the pharmaceutical formulation comprisesat least 5% of the first lipid by weight. In some embodiments, thepharmaceutical formulation comprises no more than 95% of the first lipidby weight. In some embodiments, the pharmaceutical formulation comprisesa second lipid. In some embodiments, the pharmaceutical formulationcomprises at least 5% of the second lipid by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the second lipid by weight. In some embodiments, the second lipid isomega-3. The second lipid can be any of the lipids disclose herein or amixture thereof.

Pharmaceutical formulations comprising drugs or molecules of interestcan also comprise elements that can have beneficial effects on organsthat are being treated. For example lipids and anti-oxidants can beused, which can have beneficial effects for preventing or treatingoxidative stress, fibrosis and scarring. Examples of lipids that can beincluded in the pharmaceutical formulations disclosed herein caninclude, but are not limited to, oils, emulsions, and omega-3 from fishoil, omega-3 from flaxseed, and omega-3 from walnuts. In someembodiments, the pharmaceutical formulation disclosed herein comprises anon-deuterated form of tetrahydrocurcumin. In some embodiments, thepharmaceutical formulation comprises deuterated forms oftetrahydrocurcumin, as described in several embodiments herein. In someembodiments, the pharmaceutical formulation disclosed herein comprises anon-deuterated form of tetrahydrocurcumin and a deuterated form oftetrahydrocurcumin, as described in several embodiments herein. In someembodiments, pharmaceutical formulations are provided comprising lipids.In some embodiments, the lipids are phospholipids. In some embodiments,the lipids are omega-3. In some embodiments, the lipids arepolyenylphosphatidylcholine.

Anti-oxidants, as described herein refers to a molecule that can inhibitthe oxidation of molecules and can include but is not limited toglutathione, vitamin C, vitamin A, vitamin E and alpha lipoic acid.Vitamin E acts as a peroxyl radical scavenger, and can prevent thepropagation of free radicals in tissues by reacting with free radicalsto form a tocopheryl radical, which can then be reduced by a hydrogendonor to return to its reduced state. Additionally, vitamin E is fatsoluble and can incorporate itself into cell membranes to protect themembrane lipids from oxidative damage. Vitamin C, or ascorbic acid, is aco-factor in several enzymatic reactions, and also acts as a reducingagent, reversing oxidation in liquids, and plays a role in oxidativestress. Lipoic acid, or a-lipoic acid is an antioxidant and a co-factorfor several enzymes. By adding lipids and antioxidants to drugpharmaceutical formulations, synergistic activities of the lipids andantioxidant with a drug can benefit the treatment of an organ. In someembodiments, the pharmaceutical formulation disclosed herein comprises anon-deuterated form of tetrahydrocurcumin. In some embodiments, thepharmaceutical formulation comprises deuterated forms oftetrahydrocurcumin, as described in several embodiments herein. In someembodiments, the pharmaceutical formulation disclosed herein comprises anon-deuterated form of tetrahydrocurcumin and a deuterated form oftetrahydrocurcumin, as described in several embodiments herein. In someembodiments, pharmaceutical formulations are provided comprising lipids.In some embodiments, the lipids are phospholipids. In some embodiments,the lipids are omega-3. In some embodiments, the lipids arepolyenylphosphatidylcholine. In some embodiments, a pharmaceuticalformulation is provided comprising an antioxidant. In some embodiments,the antioxidant is Vitamin E. In some embodiments, the antioxidant isvitamin C. In some embodiments, the antioxidant is alpha lipoic acid.The pharmaceutical formulations disclosed herein can comprise one ormore antioxidants. In some embodiments, the pharmaceutical formulationcomprises at least 5% of antioxidant by weight. In some embodiments, thepharmaceutical formulation comprises no more than 95% of the antioxidantby weight. In some embodiments, the pharmaceutical formulation comprisesabout 5%, 10%, 15%, 20%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%,75%, 80%, 85%, 90% 95% or any other value between these values of theantioxidant by weight.

A “dietary supplement” as described herein, refers to nutrients forgrowth and health. Without being limiting, examples of dietarysupplements can include but are not limited to baicalin, cysteamine,vitamins, curcumin, terpenoids, and pantethine. “Cysteamine” as usedherein, can refer to a chemical compound that is a stable aminothiol anddegradation metabolite of the amino acid cysteine. Cysteamine is acystine depleting agent and works by reducing the amount of cysteine ina body. “Pantethine,” as used herein, can refer to a dietary supplementthat is a dimeric form of vitamin B5. Pantethine can be used to improvea blood cholesterol profile. “Vitamins,” as used herein, refers to avital nutrient that an organism requires in small amounts for normalgrowth and development. When the organism cannot synthesize the nutrientin sufficient quantities, a vitamin is needed. Without being limiting,examples of vitamins can include vitamin A, vitamin B 1, vitamin B2,vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12,vitamin C, vitamin D, vitamin E, and vitamin K. “Baicalin,” as describedherein refers to a flavonoid that is found in several species of plantsfrom the genus Scutellaria. Baicalin is a known prolyl endopeptidaseinhibitor, a potential anti-inflammatory drug, antibacterial, ahepatoprotective drug, and has been shown to exhibit multiple activitiesagainst severe acute pancreatitis, pancreatic cancer, obesity, metabolicdisorders, and cancer.

“Terpenoids” as described herein, are a large diverse class of naturallyoccurring organic chemicals that are derived from five carbon isopreneunits assembled and modified in multiple ways. Terpenoids are a subclassof prenyllipids. They can have their methyl groups moved or removed andoxygen atoms can be added. Terpenoids are the largest group of naturalcompounds and are known to those skilled in the art of their biologicalactivities and their use in treatment of disease. Many are multicyclicthat can differ in functional groups and in their basic carbonskeletons. Several examples include but are not limited tohemiterpenoids, monoterpenoids, sesquitepenoids, diterpenoids,sesterterpenoids, triterpenoids, tetraterpenoids, and polyterpenoid.

In some embodiments, the pharmaceutical formulations can comprise adietary supplement. In some embodiments, the pharmaceutical formulationcomprises cysteamine. In some embodiments, the pharmaceuticalformulation comprises pantethine. In some embodiments, thepharmaceutical formulation comprises baicalin. In some embodiments, thepharmaceutical formulation comprises curcumin. In some embodiments, thepharmaceutical formulation disclosed herein comprises a non-deuteratedform of tetrahydrocurcumin. In some embodiments, the pharmaceuticalformulation comprises deuterated forms of tetrahydrocurcumin, asdescribed in several embodiments herein. In some embodiments, thepharmaceutical formulation disclosed herein comprises a non-deuteratedform of tetrahydrocurcumin and a deuterated form of tetrahydrocurcumin,as described in several embodiments herein.

In some embodiments, the pharmaceutical formulations disclosed hereincan comprise one or more terpenoids. In some embodiments thepharmaceutical formulation comprises one or more hemiterpenoids. In someembodiments, the pharmaceutical formulation comprises one or moremonoterpenoids. In some embodiments, the pharmaceutical formulationcomprises one or more sesquitepenoids. In some embodiments, thepharmaceutical formulation comprises one or more sesquitepenoids. Insome embodiments, the pharmaceutical formulation comprises one or morediterpenoids. In some embodiments, the pharmaceutical formulationcomprises one or more sesterterpenoids. In some embodiments, thepharmaceutical formulation comprises one or more triterpenoids. In someembodiments, the pharmaceutical formulation comprises one or moretetraterpenoids. In some embodiments, the pharmaceutical formulationcomprises one or more polyterpenoids. In some embodiments, thepharmaceutical formulation disclosed herein comprises a non-deuteratedform of tetrahydrocurcumin. In some embodiments, the pharmaceuticalformulation comprises deuterated forms of tetrahydrocurcumin, asdescribed in several embodiments herein. In some embodiments, thepharmaceutical formulation disclosed herein comprises a non-deuteratedform of tetrahydrocurcumin and a deuterated form of tetrahydrocurcumin,as described in several embodiments herein.

Half-life, as described herein, refers to the time it takes for a drugor molecule to lose half of its pharmacologic, physiologic, orradiologic activity. The drug or molecule can be a metabolite, signalingmolecule, or other substances used for treatment and are known to thoseskilled in the art. The half-life of a drug in circulation can beaffected by kidney function, the liver, and the excretory system thatcan lead the drug into the metabolic break down by enzymatic reactionsin the specific organs of drug passage, and elimination of the drug ormolecule from the body of the subject. As drug effectiveness is hamperedby its half-life, a higher dosage of drug administered to a subject inneed can be implemented, which does not increase half-life, but can benecessary in order to keep the drug in circulation for a longer periodof time and would thus be effective in increasing the bioavailability ofthe drug. However, a higher dose can also be a disadvantage, forexample, for some drugs it can lead to toxic effects in higherconcentrations of the drug.

In some embodiments, a pharmaceutical formulation or a drug can beadministered intravenously. “Intravenous therapy,” as described herein,is a route of administration to deliver fluids and medication to asubject in need directly into a vein. However, through this route thebioavailability of a drug can still be affected from enzymatic reactionsin the bloodstream.

There are several ways to improve the bioavailability of a drug bymethods of increasing the half-life. The development of introducingdeuterium into the structure of a molecule to replace hydrogen, canretain the biochemical potency and selectivity of the physiologicallyactive compound and simultaneously modify the metabolic fate in order toincrease its bioavailability in the blood stream of a subject in need.Deuteration, or the addition of a deuterium in place of hydrogen, canhelp to create drugs that can bypass quick metabolizing by the organs ofthe system compared to their hydrogenated counterparts.

“Deuterium” as described herein is a stable isotope of hydrogen in whichthe nucleus of deuterium contains one proton and one neutron. Theproperties of deuterated compounds or molecules can exhibit significantisotope effects and other physical and chemical property differences incomparison to its hydrogenated counterpart. An advantage of deuterationcan be the reduced rates of metabolism of a molecule that is deuterated,in the gut wall and or liver. Deuterated drugs or molecules can have areduced dosing requirement and produce lower metabolite loads. Therebythe deuterated compound can have reduced formation of toxic or reactivemetabolites. Although deuterium can behave similarly to hydrogen,deuterium exhibits differences in its bond energy and bond lengths forcompounds in which the heavy hydrogen isotopes have replaced hydrogen.For deuterated compounds, the bond length for bound deuterons exceedsthat of bound hydrogens. Furthermore, the deuterium-carbon bonds can besix to ten times more stable than that of a carbon-hydrogen bond,lending to a stronger bond that can be more difficult to cleave, thusslowing down the rate of bond cleavage. In effect, this kinetic isotopeeffect (KIE) can affect the biological fate of drugs that are quicklymetabolized by pathways that can involve the cleavage of hydrogen-carbonbonds. In several embodiments, methods are provided for deuteration of amolecule. In some embodiments, pharmaceutical formulations are provided.In some embodiments, the pharmaceutical formulation includes deuteratedmolecules for treatment. In some embodiments, the pharmaceuticalformulation disclosed herein comprises a non-deuterated form oftetrahydrocurcumin. In some embodiments, the pharmaceutical formulationcomprises deuterated forms of tetrahydrocurcumin, as described inseveral embodiments herein. In some embodiments, the pharmaceuticalformulation disclosed herein comprises a non-deuterated form oftetrahydrocurcumin and a deuterated form of tetrahydrocurcumin, asdescribed in several embodiments herein.

Curcuminoids are linear diarylheptanoids that are turmeric extracts usedas food coloring agents as yellow pigments, and as traditional drugs.However, as a drug curcuminoids have a poor oral bioavailability and lowplasma concentration which limits their use. The prominent metabolicpathways for the breakdown of curcuminoids are reduction and conjugationwhich lead to the molecule being excreted. Several drug metabolizingenzymes such as alcohol dehydrogenase, UDP-glucuronosyltransferases(UGTs) or sulfotransfereases (SULTs) are involved in the metabolicbreakdown of curcuminoids. Aside from this pathway, dehydroxylation,cyclization and methylation can also occur in vivo.

“Tetrahydrocurcumin,” as described herein, is a major metabolite of thecurcuminoid, curcumin and can be used for its anti-fibrotic andanti-oxidant activities. Tetrahydrocurcumin is a strong anti-oxidativemolecule, and can be obtained by the hydrogenation of curcumin.Tetrahydrocurcumin can be used as an anti-oxidant in oxidative stressdiseases. Although tetrahydrocurcumin is relatively safe at high dosages(80 mgs/kg body weight), one of the major disadvantages oftetrahydrocurcumin is its low solubility, in which it has poorsolubility in water at acidic and at physiological pH. Anotherdisadvantage is its ability to hydrolyse rapidly in basic solutions. Ina majority of current treatments, tetrahydrocurcumin is poorly absorbedand is rapidly metabolized. In order to increase the half-life oftetrahydrocurcumin, methods are provided for the deuteration oftetrahydrocurcumin. Deuteration at one or two alcohol sites oftetrahydrocurcumin can delay glucuronidation, thus improving thehalf-life of tetrahydrocurcumin. In some embodiments, a deuterated formof tetrahydrocurcumin is provided. In some embodiments, the deuteratedform of tetrahydrocurcumin has at least one deuteron. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least fifteen deuterons. Insome embodiments, the deuterated form of tetrahydrocurcumin has at leasttwenty deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least twenty four deuterons.

In some embodiments, a deuterated form of tetrahydrocurcumin isprovided. In some embodiments, the deuterated form of tetrahydrocurcuminis deuterated at one site. For example, site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 can be deuterated.

In some embodiments, tetrahydrocurcumin is deuterated at two sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15. In someembodiments, two of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at three sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,three of site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at four sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, four of site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14and site 15 in the deuterated form of tetrahydrocurcumin are deuterated.In some embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at five sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, five of site 1, site 2, site 3,site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11, site12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at six sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15. In some embodiments, the fifth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the sixth site of deuteration is at site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, six of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at seven sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, seven of site 1, site 2, site 3, site 4, site 5, site 6,site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 andsite 15 in the deuterated form of tetrahydrocurcumin are deuterated. Insome embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at eight sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eight of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at nine sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, nine of site1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site10, site 11, site 12, site 13, site 14 and site 15 in the deuteratedform of tetrahydrocurcumin are deuterated. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 hastwo deuterons. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have three deuterons. In someembodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at ten sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, ten of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at eleven sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eleven of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at twelve sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, twelve ofsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at thirteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, thirteen of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at fourteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15. In some embodiments, fourteenof site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at fifteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the fifteenth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15. In some embodiments, fifteen of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

Curcumin is a diarylheptanoid, a class of plant secondary metabolitesand can exist in both an enol form and a keto form. Tetrahydrocurcuminis derived from curcumin. Curcumin has been used and studied for itsapplications as it can have several health benefits, such asanti-carcinogenic, anti-inflammatory, antimicrobial, antioxidant,immunomodulatory, and anti-Alzheimer properties. For example curcumincan be used to reduce hyperlipidemia, delay cataract development,ameliorate renal lesions, treat cancers, immune deficiencies,cardiovascular disease, Alzheimer's diabetes, Crohn's disease, and as anantioxidant curcumin can reduce cross linking of collagen, and reduceblood glucose levels. Like tetrahydrocurcumin, curcumin is poorlyabsorbed and is rapidly metabolized. To overcome the pharmacologicalbarriers of its low bioavailability, pharmaceutical formulationscomprising curcumin as a supplement can also comprise phospholipids toincrease absorptivity of curcumin. In some embodiments, thepharmaceutical formulations disclosed herein can comprise curcumin. Insome embodiments, the curcumin is deuterated. In some embodiments,curcumin can have one, two, three, four, five, six, seven, eight, nine,ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, ortwenty-four deuterons.

In some embodiments, the pharmaceutical formulation disclosed hereincomprises a non-deuterated form of tetrahydrocurcumin. In someembodiments, the pharmaceutical formulation comprises deuterated formsof tetrahydrocurcumin, as described in several embodiments herein. Insome embodiments, the pharmaceutical formulation disclosed hereincomprises a non-deuterated form of tetrahydrocurcumin and a deuteratedform of tetrahydrocurcumin, as described in several embodiments herein.In some embodiments, the pharmaceutical formulations disclosed hereincan comprise a deuterated tetrahydrocurcumin. In some embodiments, thedeuterated form of tetrahydrocurcumin is deuterated at two alcoholsites. In some embodiments, the deuterated form of tetrahydrocurcuminhas no more than fifteen deuterated sites. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least ten deuterated sites.In some embodiments, the deuterated form of tetrahydrocurcumin has atleast five deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone, two, three, four, five, six, seven, eight, nine, ten, eleven,twelve, thirteen, fourteen, or fifteen sites. The tetrahydrocurcumin canbe deuterated, for example, at an alcohol site. In some embodiments, thetetrahydrocurcumin is deuterated at one or two alcohol sites. As shownin FIG. 1, some deuteration sites can have one, two, or three deuterons.For example, in FIG. 1, deuteration site 1 can have one deuteron;deuteration site 2 refers to the methyl group which can have one, two orthree deuterons (e.g., deuteration sites 2a, 2b, and 2c); deuterationsite 12 refers to the methyl group which can have one, two or threedeuterons (deuteration sites 12a, 12b, and 12c); deuteration sites 6, 7,8, 9 and 10 can have one or two deuterons (deuteration sites 6a and 6b,7a and 7b, 8a and 8b, 9a and 9b, and 10a and 10b). The two alcohol sitesof tetrahydrocurcumin at sites 3 and 13 are sites that can increase thehalf-life of tetrahydrocurcumin. In some embodiments, the deuteratedform of tetrahydrocurcumin is deuterated at sites 3 and 13.

Tetrahydrocurcumin has fifteen deuteration sites, some of which can haveone, two or three deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least five deuterons. Insome embodiments, the deuterated form of tetrahydrocurcumin has at leastten deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least fifteen deuterons. In some embodiments,the deuterated form of tetrahydrocurcumin has at least twenty deuterons.In some embodiments, the deuterated form of tetrahydrocurcumin has atleast twenty-four deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two,twenty-three, or twenty-four deuterons.

In some embodiments, a pharmaceutical formulation comprising adeuterated form of tetrahydrocurcumin is provided. In some embodiments,the pharmaceutical formulation comprises a pharmaceutical vehicle.“Pharmaceutical vehicle” as described herein refers to an inertsubstance with which a medication is mixed to facilitate measurement andadministration of the pharmaceutical formulation. In some embodimentsthe tetrahydrocurcumin is deuterated. In some embodiments, thedeuterated form of tetrahydrocurcumin is deuterated at one site. Forexample, site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 can bedeuterated.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at two sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15. In someembodiments, two of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at three sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,three of site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at four sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, four of site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14and site 15 in the deuterated form of tetrahydrocurcumin are deuterated.In some embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at five sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, five of site 1, site 2, site 3,site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11, site12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at six sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15. In some embodiments, the fifth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the sixth site of deuteration is at site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, six of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at seven sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, seven of site 1, site 2, site 3, site 4, site 5, site 6,site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 andsite 15 in the deuterated form of tetrahydrocurcumin are deuterated. Insome embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at eight sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eight of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at nine sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, nine of site1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site10, site 11, site 12, site 13, site 14 and site 15 in the deuteratedform of tetrahydrocurcumin are deuterated. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 hastwo deuterons. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have three deuterons. In someembodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at ten sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, ten of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at eleven sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eleven of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at twelve sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, twelve ofsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at thirteen sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, thirteen of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at fourteen sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15. In some embodiments, fourteenof site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, pharmaceutical formulations disclosed herein cancomprise tetrahydrocurcumin deuterated at fifteen sites. In someembodiments, at least one of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the fifteenth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15. In some embodiments, fifteen of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

Pharmaceutical Formulations

In some embodiments, the active ingredients and mixtures of activeingredients can be used, for example, in pharmaceutical formulationscomprising a pharmaceutically acceptable carrier prepared for storageand subsequent administration. Also, some embodiments include use of theabove-described active ingredients with a pharmaceutically acceptablecarrier or diluent. Acceptable carriers or diluents for therapeutic useare well known in the pharmaceutical art, and are described, forexample, in Remington's Pharmaceutical Sciences, 18th Ed., MackPublishing Co., Easton, Pa. (1990), which is incorporated herein byreference in its entirety. Preservatives, stabilizers, dyes and evenflavoring agents can be provided in the pharmaceutical formulation. Forexample, sodium benzoate, ascorbic acid and esters of p-hydroxybenzoicacid can be added as preservatives. In addition, antioxidants andsuspending agents can be used.

Pharmaceutical formulations of the active ingredients can be formulatedand used as tablets, capsules, or elixirs for oral administration;suppositories for rectal administration; sterile solutions, suspensionsfor injectable administration; patches for transdermal administration,and sub-dermal deposits and the like. Injectables can be prepared inconventional forms, either as liquid solutions or suspensions, solidforms suitable for solution or suspension in liquid prior to injection,or as emulsions. Suitable excipients are, for example, water, saline,dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate,cysteine hydrochloride, and the like. In addition, if desired, theinjectable pharmaceutical formulations can contain minor amounts ofnontoxic auxiliary substances, such as wetting agents, pH bufferingagents, and the like. If desired, absorption enhancing preparations (forexample, liposomes), can be utilized.

For injection, the agents of the invention can be formulated in aqueoussolutions, preferably in physiologically compatible buffers such asHanks' solution, Ringer's solution, or physiological saline buffer. Forsuch transmucosal administration, penetrants appropriate to the barrierto be permeated are used in the formulation. Such penetrants aregenerally known in the art. Use of pharmaceutically acceptable carriersto formulate the ingredients herein disclosed for the practice of theinvention into dosages suitable for systemic administration is withinthe scope of the invention. With proper choice of carrier and suitablemanufacturing practice, the pharmaceutical formulations disclosedherein, in particular, those formulated as solutions, can beadministered parenterally, such as by intravenous injection. The activeingredients can be formulated readily using pharmaceutically acceptablecarriers well known in the art into dosages suitable for oraladministration. Such carriers enable the compounds of the invention tobe formulated as tablets, pills, capsules, liquids, gels, syrups,slurries, suspensions and the like, for oral ingestion by a patient tobe treated.

Pharmaceutical formulations for parenteral administration includeaqueous solutions of the active ingredients in water-soluble form.Additionally, suspensions of the active ingredients can be prepared asappropriate oily injection suspensions. Suitable lipophilic solvents orvehicles include fatty oils such as sesame oil, or other organic oilssuch as soybean, grapefruit or almond oils, or synthetic fatty acidesters, such as ethyl oleate or triglycerides, or liposomes. Aqueousinjection suspensions can contain substances which increase theviscosity of the suspension, such as sodium carboxymethyl cellulose,sorbitol, or dextran. Optionally, the suspension can also containsuitable stabilizers or agents that increase the solubility of theingredients to allow for the preparation of highly concentratedsolutions. In some embodiments, of the pharmaceutical formulations, thevehicle is a lipophilic solvent, fatty oil, organic oil, or liposome. Insome embodiments, the vehicle is sesame oil, soybean, grapefruit oralmond oils, or synthetic fatty acid esters, such as ethyl oleate ortriglycerides, or liposomes.

Pharmaceutical preparations for oral use can be obtained by combiningthe active ingredients with solid excipient, optionally grinding aresulting mixture, and processing the mixture of granules, after addingsuitable auxiliaries, if desired, to obtain tablets or dragee cores.Suitable excipients are, in particular, fillers such as sugars,including lactose, sucrose, mannitol, or sorbitol; cellulosepreparations such as, for example, maize starch, wheat starch, ricestarch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP). If desired, disintegrating agents can beadded, such as the cross-linked polyvinyl pyrrolidone, agar, or alginicacid or a salt thereof such as sodium alginate. Dragee cores areprovided with suitable coatings. For this purpose, concentrated sugarsolutions can be used, which can optionally contain gum arabic, talc,polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/ortitanium dioxide, lacquer solutions, and suitable organic solvents orsolvent mixtures. Dyestuffs or pigments can be added to the tablets ordragee coatings for identification or to characterize differentcombinations of active ingredient doses. For this purpose, concentratedsugar solutions can be used, which can optionally contain gum arabic,talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/ortitanium dioxide, lacquer solutions, and suitable organic solvents orsolvent mixtures. Dyestuffs or pigments can be added to the tablets ordragee coatings for identification or to characterize differentcombinations of active ingredient doses. Such formulations can be madeusing methods known in the art. See, for example, U.S. Pat. No.5,733,888 (injectable pharmaceutical formulations); U.S. Pat. No.5,726,181 (poorly water soluble compounds); U.S. Pat. No. 5,707,641(therapeutically active proteins or peptides); U.S. Pat. No. 5,667,809(lipophilic agents); U.S. Pat. No. 5,576,012 (solubilizing polymericagents); U.S. Pat. No. 5,707,615 (anti-viral formulations); U.S. Pat.No. 5,683,676 (particulate medicaments); U.S. Pat. No. 5,654,286(topical formulations); U.S. Pat. No. 5,688,529 (oral suspensions); U.S.Pat. No. 5,445,829 (extended release formulations); U.S. Pat. No.5,653,987 (liquid formulations); U.S. Pat. No. 5,641,515 (controlledrelease formulations) and U.S. Pat. No. 5,601,845 (spheroidformulations); all of which are incorporated herein by reference intheir entireties. The pharmaceutical formulations can be manufactured ina manner that is itself known, for example, by means of conventionalmixing, dissolving, granulating, dragee-making, levitating, emulsifying,encapsulating, entrapping, or lyophilizing processes. In someembodiments, the pharmaceutical formulation further comprises anexcipient. In some embodiments, the pharmaceutical formulation isprepared for oral use. In some embodiments, the excipient is sugars,including lactose, sucrose, mannitol, or sorbitol; cellulosepreparations such as, for example, maize starch, wheat starch, ricestarch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP).

To formulate the dosage including one or more active ingredientsdisclosed herein, known surface active agents, excipients, smoothingagents, suspension agents and pharmaceutically acceptable film-formingsubstances and coating assistants, and the like can be used. Preferablyalcohols, esters, sulfated aliphatic alcohols, and the like can be usedas surface active agents; sucrose, glucose, lactose, starch,crystallized cellulose, mannitol, light anhydrous silicate, magnesiumaluminate, magnesium methasilicate aluminate, synthetic aluminumsilicate, calcium carbonate, sodium acid carbonate, calcium hydrogenphosphate, calcium carboxymethyl cellulose, and the like can be used asexcipients; magnesium stearate, talc, hardened oil and the like can beused as smoothing agents; coconut oil, olive oil, sesame oil, peanutoil, soya can be used as suspension agents or lubricants; celluloseacetate phthalate as a derivative of a carbohydrate such as cellulose orsugar, or methylacetate-methacrylate copolymer as a derivative ofpolyvinyl can be used as suspension agents; and plasticizers such asester phthalates and the like can be used as suspension agents. Inaddition to the foregoing ingredients, sweeteners, fragrances,colorants, preservatives and the like can be added to the administeredformulation of the compound of the invention, particularly when thecompound is to be administered orally.

Further disclosed herein are various pharmaceutical formulations wellknown in the pharmaceutical art for uses that include intraocular,intranasal, and intraauricular delivery. Pharmaceutical formulationsinclude aqueous ophthalmic solutions of the active ingredients inwater-soluble form, such as eyedrops, or in gellan gum (Shedden et al.,Clin. Ther., 23(3):440-50 (2001)) or hydrogels (Mayer et al.,Ophthalmologica, 210(2):101-3 (1996)); ophthalmic ointments; ophthalmicsuspensions, such as microparticulates, drug-containing small polymericparticles that are suspended in a liquid carrier medium (Joshi, A., J.Ocul. Pharmacol., 10(1):29-45 (1994)), lipid-soluble formulations (Almet al., Prog. Clin. Biol. Res., 312:447-58 (1989)), and microspheres(Mordenti, Toxicol. Sci., 52(1):101-6 (1999)); and ocular inserts. Allof the above-mentioned references are incorporated herein by referencein their entireties. Such suitable pharmaceutical formulations are mostoften and preferably formulated to be sterile, isotonic and buffered forstability and comfort. Pharmaceutical formulations can also includedrops and sprays often prepared to simulate in many respects nasalsecretions to ensure maintenance of normal ciliary action. As disclosedin Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing Co.,Easton, Pa. (1990), which is incorporated herein by reference in itsentirety, and well-known to those skilled in the art, suitableformulations are most often and preferably isotonic, slightly bufferedto maintain a pH of 5.5 to 6.5, and most often and preferably includeantimicrobial preservatives and appropriate drug stabilizers.Pharmaceutical formulations for intraauricular delivery includesuspensions and ointments for topical application in the ear. Commonsolvents for such aural formulations include glycerin and water.

The pharmaceutical formulations described herein can be administered byeither oral or non-oral pathways. When administered orally,pharmaceutical formulations can be administered in capsule, tablet,granule, spray, syrup, or other such form. Pharmaceutical formulationsalso can be brewed, as with a tea, or formed by dissolving a powderedpharmaceutical formulation into a fluid, typically water, fruit orvegetable juice, or milk. When administered non-orally, it can beadministered as an aqueous suspension, an oily preparation or the likeor as a drip, suppository, salve, ointment or the like, whenadministered via injection, subcutaneously, intreperitoneally,intravenously, intramuscularly, or the like. Similarly, it can beadministered topically, rectally, or vaginally, as deemed appropriate bythose of skill in the art for bringing the ingredients of the inventioninto optimal contact with living tissue.

Agents intended to be administered intracellularly can be administeredusing techniques well known to those of ordinary skill in the art. Forexample, such agents can be encapsulated into liposomes, thenadministered by any of the methods described herein. All moleculespresent in an aqueous solution at the time of liposome formation areincorporated into the aqueous interior. The liposomal contents are bothprotected from the external micro-environment and, because liposomesfuse with cell membranes, are efficiently delivered into the cellcytoplasm. Additionally, due to their hydrophobicity, small organicmolecules can be directly administered intracellularly.

In some embodiments, the pharmaceutical formulations described hereinare formulated into a single pill or tablet. In some embodiments, thepill or tablet has a mass from 10 mg to 2000 mg. In some embodiments,the pill or tablet has a mass from 100 mg to 1500 mg. In someembodiments, the pill or tablet has a mass from 500 mg to 1200 mg. Insome embodiments, the pill or tablet has a mass from 800 mg to 1100 mg.

Methods of Administration

Some embodiments also encompass methods for making and for administeringthe disclosed pharmaceutical formulations. Such disclosed methodsinclude, among others, (a) administration through oral pathways, whichadministration includes administration in capsule, tablet, granule,spray, syrup, or other such forms; (b) administration through non-oralpathways, which administration includes administration as an aqueoussuspension, an oily preparation or the like or as a drip, suppository,salve, ointment or the like; administration via injection,subcutaneously, intraperitoneally, intravenously, intramuscularly,intradermally, or the like; as well as (c) administration topically, (d)administration rectally, or (e) administration vaginally, as deemedappropriate by those of skill in the art for bringing the compound ofthe invention into contact with living tissue; and (f) administrationvia controlled released formulations, depot formulations, and infusionpump delivery. As further examples of such modes of administration andas further disclosure of modes of administration, disclosed herein arevarious methods for administration of the disclosed pharmaceuticalformulations including modes of administration through intraocular,intranasal, and intraauricular pathways.

The pharmaceutically effective amount of the ingredients disclosedherein required as a dose will depend on the route of administration andthe physical characteristics of the specific human under consideration.The dose can be tailored to achieve a desired effect, but will depend onsuch factors as weight, diet, concurrent medication and other factors,which those skilled in the medical arts will recognize.

In practicing the methods of the invention, the products orpharmaceutical formulations can be used alone or in combination with oneanother or in combination with other therapeutic or diagnostic agents.These products can be utilized in vivo, ordinarily in a mammal,preferably in a human, or in vitro. In employing them in vivo, theproducts or pharmaceutical formulations can be administered to themammal in a variety of ways, including parenterally, intravenously,subcutaneously, intramuscularly, colonically, rectally, vaginally,nasally or intraperitoneally, employing a variety of dosage forms. Suchmethods can also be applied to testing chemical activity in vivo.

As will be readily apparent to one skilled in the art, the useful invivo dosage to be administered and the particular mode of administrationwill vary depending upon the age, weight and mammalian species treated,the particular ingredients employed, and the specific use for whichthese ingredients are employed. The determination of effective dosagelevels, that is the dosage levels necessary to achieve the desiredresult, can be accomplished by one skilled in the art using routinepharmacological methods. Typically, human clinical applications ofproducts are commenced at lower dosage levels, with dosage level beingincreased until the desired effect is achieved. Alternatively,acceptable in vitro studies can be used to establish useful doses androutes of administration of the pharmaceutical formulations identifiedby the present methods using established pharmacological methods. Innon-human animal studies, applications of potential products arecommenced at higher dosage levels, with dosage being decreased until thedesired effect is no longer achieved or adverse side effects disappear.

The dosage of active ingredient(s) can range broadly, depending upon thedesired affects and the therapeutic indication. Typically, dosages ofactive ingredient(s) can be between about 10 microgram/kg and 100 mg/kgbody weight, preferably between about 100 microgram/kg and 10 mg/kg bodyweight. Alternatively dosages can be based and calculated upon thesurface area of the patient, as understood by those of skill in the art.Administration is preferably oral on a daily or twice daily basis. Insome embodiments, the active ingredient in the pharmaceuticalformulation of any of the embodiments described herein is non-deuteratedor deuterated form of tetrahydrocurcumin. In some embodiments, theactive ingredient(s) can be between about 10 microgram/kg and 100 mg/kgbody weight, preferably between about 100 microgram/kg and 10 mg/kg bodyweight.

The exact formulation, route of administration and dosage can be chosenin view of the consumer's condition. See for example, Fingl et al., inThe Pharmacological Basis of Therapeutics, 1975, which is incorporatedherein by reference in its entirety. The magnitude of an administrateddose can vary with the severity of a particular medical or physicalcondition and the route of administration. The severity of a conditioncan, for example, be evaluated, in part, by standard prognosticevaluation methods. Further, the dose and perhaps dose frequency canalso vary according to the age, body weight, and response of theindividual. A program comparable to that discussed herein can be used inveterinary medicine.

A variety of techniques for formulation and administration can be foundin Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing Co.,Easton, Pa. (1990), which is incorporated herein by reference in itsentirety. Suitable administration routes can include oral, rectal,transdermal, vaginal, transmucosal, or intestinal administration;parenteral delivery, including intramuscular, subcutaneous,intramedullary injections, as well as intrathecal, directintraventricular, intravenous, intraperitoneal, intranasal, orintraocular injections.

The combined active ingredients in the pharmaceutical formulationsdisclosed herein can be orally or non-orally administered to a humanpatient in the amount of about 0.0007 mg/day to about 7,000 mg/day ofthe total active ingredients, and more preferably about 0.07 mg/day toabout 70 mg/day of the total active ingredients at, one time per day orin other embodiments, over two to about ten times per day.Alternatively, the active ingredients disclosed herein can beadministered in the stated amounts continuously by, for example, anintravenous drip. Thus, for a patient weighing 70 kilograms, thepreferred daily dose of the total active ingredients would be about0.0007 mg/kg/day to about 35 mg/kg/day, and more preferable, 0.007mg/kg/day to about 15 mg/kg/day. Nonetheless, as will be understood bythose of skill in the art, in certain situations it can be necessary toadminister the active ingredients disclosed herein in amounts thatexcess, or even far exceed, the above-stated, preferred dosage range totreat effectively and aggressively a desired condition orcharacteristic.

In some embodiments, the pharmaceutical formulations disclosed hereincan be orally or non-orally administered to a human patient in theamount of about 0.0007 mg/day to about 7,000 mg/day of the total activeingredients, and more preferably about 0.07 mg/day to about 70 mg/day ofthe total active ingredients at, one time per day or in otherembodiments, over two to about ten times per day. In some embodiments,the preferred daily dose of the total active ingredients would be about0.0007 mg/kg/day to about 35 mg/kg/day, and more preferable, 0.007mg/kg/day to about 15 mg/kg/day.

Ingredients disclosed herein can be evaluated for efficacy and toxicityusing known methods. For example, the toxicology of a particularcompound or ingredient, or of a subset of the compounds, sharing certainchemical moieties, can be established by determining in vitro toxicitytowards a cell line, such as a mammalian, and preferably a human, cellline. The results of such studies are often predictive of toxicity inanimals, such as mammals, or more specifically, humans. Alternatively,the toxicity of particular compounds or ingredients in an animal model,such as mice, rats, rabbits, or monkeys, may be determined using knownmethods. The efficacy of a particular compound may be established usingseveral recognized methods, such as in vitro methods, animal models, orhuman clinical trials. Recognized in vitro models exist for nearly everyclass of condition, including the conditions abated by the compounds oringredients disclosed herein, including obesity. Similarly, acceptableanimal models may be used to establish efficacy of chemicals to treatsuch conditions. When selecting a model to determine efficacy, theskilled artisan can be guided by the state of the art to choose anappropriate model, dose, and route of administration, and regime. Ofcourse, human clinical trials can also be used to determine the efficacyof a compound or ingredient in humans.

The active ingredients described herein may be used alone or incombination with one another, or in combination with other therapeuticor diagnostic agents. These products can be utilized in vivo or invitro. The useful dosages and the most useful modes of administrationwill vary depending upon the age and weight of the consumer, theparticular ingredients employed, and the specific use for which theseingredients are employed.

In some embodiments, a method for making deuterated tetrahydrocurcuminis provided. The concept of deuteration of tetrahydrocurcumin is similarto that of the deuteration of dimethylcurcumin, in which the deuterationconcept is described, for example, in U.S. Pat. No. 8,575,221 B2, whichis hereby incorporated by reference in its entirety. The method cancomprise contacting tetrahydrocurcumin in the presence of a catalyst anddeuterated water under a condition to form the deuterated form oftetrahydrocurcumin. The method can further comprise hydrogenatingcurcumin to form the tetrahydrocurcumin. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least one deuterated site.In some embodiments, the deuterated form of tetrahydrocurcumin has atleast five deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has fifteendeuterated sites or an amount less fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two,twenty-three, or twenty-four deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin is deuterated at one or twoalcohol sites.

In some embodiments, a method for making deuterated tetrahydrocurcuminis provided. In some embodiments, tetrahydrocurcumin is deuterated atone site. In some embodiments, site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 or site 15 is deuterated.

In some embodiments, tetrahydrocurcumin is deuterated at two sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15. In someembodiments, two of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at three sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,three of site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at four sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, four of site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14and site 15 in the deuterated form of tetrahydrocurcumin are deuterated.In some embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at five sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, five of site 1, site 2, site 3,site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11, site12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at six sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15. In some embodiments, the fifth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the sixth site of deuteration is at site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, six of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at seven sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, seven of site 1, site 2, site 3, site 4, site 5, site 6,site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 andsite 15 in the deuterated form of tetrahydrocurcumin are deuterated. Insome embodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at eight sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eight of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at nine sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, nine of site1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site10, site 11, site 12, site 13, site 14 and site 15 in the deuteratedform of tetrahydrocurcumin are deuterated. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 hastwo deuterons. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have three deuterons. In someembodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at ten sites. Insome embodiments, at least one of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, ten of site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 and site15 in the deuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at eleven sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, eleven of site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 and site 15 in the deuterated form oftetrahydrocurcumin are deuterated. In some embodiments, a deuteratedsite in the deuterated form of tetrahydrocurcumin can have twodeuterons. In some embodiments, site 2, 6, 7, 8, 9, 10, or 12 has twodeuterons. In some embodiments, a deuterated site in the deuterated formof tetrahydrocurcumin can have three deuterons. In some embodiments,site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at twelve sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, twelve ofsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havetwo deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at thirteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, thirteen of site 1, site 2, site 3, site 4, site 5,site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at fourteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15. In some embodiments, fourteenof site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site9, site 10, site 11, site 12, site 13, site 14 and site 15 in thedeuterated form of tetrahydrocurcumin are deuterated. In someembodiments, a deuterated site in the deuterated form oftetrahydrocurcumin can have two deuterons. In some embodiments, site 2,6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, tetrahydrocurcumin is deuterated at fifteen sites.In some embodiments, at least one of site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 and site 15 in the deuterated form of tetrahydrocurcumin isdeuterated. In some embodiments, the second site of deuteration is atsite 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8, site 9,site 10, site 11, site 12, site 13, site 14 or site 15 in the deuteratedform of tetrahydrocurcumin. In some embodiments, the third site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15 in the deuterated form of tetrahydrocurcumin. In some embodiments,the fourth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fifth site of deuteration is at site 1, site 2,site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the sixth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the seventhsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eighth site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the ninth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, the tenthsite of deuteration is at site 1, site 2, site 3, site 4, site 5, site6, site 7, site 8, site 9, site 10, site 11, site 12, site 13, site 14or site 15 in the deuterated form of tetrahydrocurcumin. In someembodiments, the eleventh site of deuteration is at site 1, site 2, site3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site 11,site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the twelfth site of deuterationis at site 1, site 2, site 3, site 4, site 5, site 6, site 7, site 8,site 9, site 10, site 11, site 12, site 13, site 14 or site 15 in thedeuterated form of tetrahydrocurcumin. In some embodiments, thethirteenth site of deuteration is at site 1, site 2, site 3, site 4,site 5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site13, site 14 or site 15 in the deuterated form of tetrahydrocurcumin. Insome embodiments, the fourteenth site of deuteration is at site 1, site2, site 3, site 4, site 5, site 6, site 7, site 8, site 9, site 10, site11, site 12, site 13, site 14 or site 15 in the deuterated form oftetrahydrocurcumin. In some embodiments, the fifteenth site ofdeuteration is at site 1, site 2, site 3, site 4, site 5, site 6, site7, site 8, site 9, site 10, site 11, site 12, site 13, site 14 or site15. In some embodiments, fifteen of site 1, site 2, site 3, site 4, site5, site 6, site 7, site 8, site 9, site 10, site 11, site 12, site 13,site 14 and site 15 in the deuterated form of tetrahydrocurcumin aredeuterated. In some embodiments, a deuterated site in the deuteratedform of tetrahydrocurcumin can have two deuterons. In some embodiments,site 2, 6, 7, 8, 9, 10, or 12 has two deuterons. In some embodiments, adeuterated site in the deuterated form of tetrahydrocurcumin can havethree deuterons. In some embodiments, site 2 or 12 has three deuterons.

In some embodiments, the method can include a metal catalyst. Examplesof metal catalysts include but are not limited to palladium on carbon,palladium barium carbonate, palladium barium sulphate, palladium silica,palladium alumina, platinum on carbon, platinum-palladium carbon,platinum alumina, platinum calcium carbonate, platinum barium sulfate,platinum silica, and platinum graphite. In some embodiments, thedeuterated water can be 25% deuterated, 50% deuterated, 75% deuterated,100% deuterated, or any other value between any of these values. In someembodiments, the catalyst is palladium on carbon. In some embodiments,the catalyst is palladium barium carbonate. In some embodiments, thecatalyst is palladium barium sulphate. In some embodiments, the catalystis palladium silica. In some embodiments, the catalyst is platinum oncarbon. In some embodiments, the catalyst is platinum-palladium carbon.In some embodiments, the catalyst is platinum alumina. In someembodiments, the catalyst is platinum calcium carbonate. In someembodiments, the catalyst is platinum barium sulfate. In someembodiments, the catalyst is platinum silica. In some embodiments, thecatalyst is platinum graphite. In some embodiments, the deuterated wateris at least 25% deuterated. In some embodiments, the deuterated water isat least 50% deuterated. In some embodiments, the deuterated water is atleast 75% deuterated. In some embodiments, the deuterated water is 100%deuterated.

Purification of tetrahydrocurcumin can be performed to remove thebyproducts produced from the hydrogenation of curcumin. Separation oftetrahydrocurcumin can be performed, for example, by columnchromatography. Column chromatography can include techniques such asreverse phase HPLC. In some embodiments, tetrahydrocurcumin is purifiedby column chromatography. The methods of synthesis of deuteratedtetrahydrocurcumin can be prepared by a person skilled in the art usingprocedures with appropriate concentrations of deuterated reagents. Insome embodiments, the curcumin is hydrogenated to tetrahydrocurcuminfollowed by deuteration. Additional methods for synthesizing deuteratedtetrahydrocurcumin that are not schematically shown herein are known topersons skilled in the art. In some embodiments, the method furthercomprises purifying the deuterated form of tetrahydrocurcumin. In someembodiments, the purifying step comprises isolating the deuterated formof tetrahydrocurcumin with column chromatography.

The anti-oxidant effects of tetrahydrocurcumin can be used foratherosclerotic lesion, several types of cancers, prevention of type IIdiabetes, and protection of organs from oxidative damage, such as theheart, kidney and liver. Without being limiting, several cancers caninclude, basal cell carcinoma, bile duct cancer, bone cancer, brain stemglioma, breast cancer, Burkitt Lymphoma, cervical cancer, colon cancer,colorectal cancer, cutaneous T-cell lymphoma, ductal carcinoma,endometrial cancer, esophageal cancer, Ewing sarcoma, retinoblastoma,gallbladder cancer, gastric cancer, kidney cancer, liver cancer,pancreatic cancer, leukemia, lung cancer, melanoma, ovarian cancer, skincancer, and stomach cancer. In some embodiments, the non-deuterated ordeuterated form of tetrahydrocurcumin in a pharmaceutical formulationcan be used to treat atherosclerotic lesion, several types of cancers ortype II diabetes as a therapy.

“Atherosclerosis” as described herein, refers to the thickening of theartery wall which can be the results of dead cells, damage from highcholesterol, triglycerides, and plaques. Atherosclerosis can lead to theatherosclerotic lesions cab be considered advanced when there are a highaccumulation of lipid, cells, and matrix pharmaceutical formulationswhich can narrow the arterial lumen and become clinically significant,leading to complications. In some embodiments, methods are provided fortreating, inhibiting, or ameliorating a disorder in a subject. In someembodiments, the subject suffers from atherosclerosis.

Cancer can refer to a group of diseases that can involve abnormal cellgrowth that invades and spreads within a body. To date there are overone hundred types of cancer, in which systems and states depend upon thetype of cancer. Current treatment for cancer can include chemotherapy,radiation, drug therapy, and surgical procedures. The anti-oxidanteffect of tetrahydrocurcumin can be used to treat several types ofcancers. In some embodiments, methods are provided for treating,inhibiting, or ameliorating a disorder in a subject. In someembodiments, the subject suffers from cancer.

“Type II diabetes,” as described herein refers to a metabolic disorderthat is characterized by hyperglycemia, insulin resistance, and therelative lack of insulin. Subjects suffering from Type II diabetes cansynthesize insulin, however either the pancreas cannot make enoughinsulin, or the body of the subject cannot use insulin. Insulinresistance can refer to the lack of insulin or the inability to use theinsulin, leading to a high level of glucose in the blood leading todetrimental effects in the subject. High levels of blood sugar can leadto nerve damage, small blood vessel damage, organ damage,atherosclerosis, arterial hardening, heart attack and stroke. Type IIdiabetes with hyperlipidemia, can involve abnormally elevated levels oflipids and lipoproteins in the blood which can be due to genetic causes.In diabetes, the liver and the kidney play a major role in thepathogenesis of the disease. The liver enzymes aspartate transaminase,alanine transaminase, alkaline phosphates, and γ-glutamyl transpeptidaseare used for assessing liver function, in which they are elevated inpatients with liver diseases. In some embodiments, methods are providedfor treating, inhibiting, or ameliorating a disorder in a subject. Insome embodiments, the subject suffers from Type II diabetes.

In several studies, tetrahydrocurcumin was shown to decrease the levelsof plasma total protein, albumin, globulin and albumin/globulin ratio.Additionally, hepatic and renal markers that are elevated in diabeticmice were significantly lowered in the presence of tetrahydrocurcumin.Administration of tetrahydrocurcumin can normalize blood glucose andcause an improvement of altered carbohydrate metabolic enzymes.Furthermore, tetrahydrocurcumin can cause a significant increase in theactivities of superoxide dismutase, catalase, glutathione peroxidase,glutathione S-transferase, reduced glutathione, vitamin C and vitamin Ein the liver or diabetic rats, indicating a role of tetrahydrocurcuminin preventing lipid peroxidation induced membrane damage. Moreimportantly tetrahydrocurcumin has been shown to have an antioxidanteffect in addition to an anti-diabetic effect in Type II diabetes. Inview of tetrahydrocurcumins potential compared to Silymarin, a liverprotective substance known to increase glutathione production in theliver, tetrahydrocurcumin was shown to have better protection againstlipid peroxidation. However in view of the bioavailability oftetrahydrocurcumin and curcumin and their ability to be quicklymetabolized, improved pharmaceutical formulations are needed in order toallow absorption and stability in a subject being treated, to avoidrapid metabolizing of the drug before it reaches its target organ. Insome embodiments, treating, inhibiting, or ameliorating a disorder in asubject is provided. A disorder, as used herein, can refer to acondition that interferes with cells, tissues, and organs. In someembodiments, the subject suffers from diabetes. In some embodiments, thesubject suffers from Type II diabetes with hyperlipidemia.

“Hypertension,” as described herein, is a chronic medical condition inwhich blood pressure in the arteries is elevated. Hypertension putsstrain on the heart and can lead to hypertensive heart disease, andcoronary heart disease. Hypertension can lead to stroke, aneurysms,peripheral arterial disease and can be a causative factor for chronickidney disease. Left ventricular hypertrophy in hypertension can reflectphysiological adaptation to increased work load of the heart and is astrong risk factor for future cardiac events such as sudden cardiacdeath. ROS and oxidative stress can also lead into the genesis ofhypertension due to hypertensive stimuli which can also promote theproduction of ROS in the brain, kidney and vasculature structure. Insome embodiments, methods are provided for treating, inhibiting, orameliorating a disorder in a subject. In some embodiments, the subjectsuffers from hypertension. In some embodiments, the subject suffers fromhypertension with left ventricular hypertrophy. Galectin-3, as describedherein, is a protein lectin that has been demonstrated to be involved inpulmonary hypertension, hypertension, cancer, inflammation, fibrosis,heart disease and stroke. In some embodiments, the subject has elevatedGalectin-3 levels in the blood. In some embodiments, the subject hasheart failure. In some embodiments, the subject has heart disease.

Oxidative damage in a subject can refer to damage that is caused by thepresence of reactive oxygen species (ROS) and the inability of abiological system to detoxify the reactive intermediates or repair theresulting damage. The production of peroxides and free radicals cancause damage to major components of a biological system and can includebut is not limited to proteins, lipids, DNA, RNA, tissues, and organs.Organs can also be damaged by the effects of ROS and other types of freeradical production leading to organ atrophy and organ dysfunction.Organs can include but are not limited to the heart, lung, kidney,liver, brain and abdominal organs. In some embodiments, methods areprovided for protecting an organ in a subject. In some embodiments, theorgan is kidney. In some embodiments, the organ is liver. In someembodiments, the subject has a liver disorder. In some embodiments, thesubject has a fatty liver disease. In some embodiments, the subject hasalcoholic liver disease. In some embodiments, the subject has a kidneydisease. In some embodiments, the subject has diabetic kidney disease.In some embodiments, the subject has polycystic kidney disease. In someembodiments, the subject has heart failure.

Reactive oxygen species has also been implicated in multiple pathologiessuch as hypertension, atherosclerosis, and diabetes. In someembodiments, the subject has hypertension. In some embodiments, thesubject has hypertension with left ventricular hypertrophy. In someembodiments, the subject has diabetes. In some embodiments, the subjecthas diabetes with hyperlipidemia. In some embodiments, the subject haselevated levels of fibrotic markers. In some embodiments, the fibroticmarkers are in blood. In some embodiments, the fibrotic markers are inurine. In some embodiments, the subject has elevated markers ofoxidative stress. The reactive oxidative stress can be involved indiseases, cancers, Parkinson's disease, Alzheimer's disease,atherosclerosis, heart failure, vitiligo, and chronic fatigue syndrome.Oxidative stress can be caused by the excess generation of ROS, freeradical production, or a decrease in endogenous antioxidant defenses.ROS and reactive nitrogen species (RNS) can be the products of cellularmetabolism and other sources of stress that together can serve asdeleterious or even beneficial species, for example the increase of freeradicals to stimulate an immune response. Oxidative stress that can leadto the production of free radicals can be caused by many factors, forexample, excessive exercise, diet, medications, glycation, diseases,environment, toxins, excessive alcohol consumption, long term smoking,diabetes, cancers, and autoimmune diseases. For example, in the case ofdiabetes, free radicals can be formed by glucose oxidation,non-enzymatic glycation of proteins, and oxidative degradation ofglycated proteins. The abnormally high level of free radicals anddecline of an antioxidant defense system can thus lead to damage ofcellular proteins and organelles, increase in lipid peroxidation and thedevelopment of insulin resistance.

Tetrahydrocurcumin can be used to treat renal damage, hepatotoxicity,and hepatic damage. Damage to the renal and hepatic tissue can occurfrom analgesics, cancers, free radical damage, and long-term drug use,for example treatment for malaria. However, due to the lowbioavailability of curcuminoids such as curcumin and tetrahydrocurcumin,the drugs are easily passed through the system and rapidly metabolizedas well. In embodiments described herein, methods are provided fortreating organ damage. In some embodiments, organ damage can arise fromanalgesics, cancers, free radical damage, and long-term drug use such asuse of anti-malarial drugs. In some embodiments, methods are providedfor treating, inhibiting, or ameliorating a disorder in a subject. Insome embodiments, the subject suffers from renal damage. In someembodiments, the subject suffers from hepatic damage. In someembodiments, the subject suffers from hepatotoxicity. In someembodiments, the subject is human. In some embodiments, the subject istaking analgesics. In some embodiments, the subject is under treatmentwith one or more anti-malarial drugs.

Subjects experiencing the damage caused by ROS or other types of freeradical species can be identified through the identification of higherlevels of oxidative stress biomarkers. Examples of biomarkers foroxidative stress include but are not limited to superoxide dismutase,catalase, glutathione reductase, glutathione peroxidase, glutathionelevels, vitamins, lipid peroxidation, nitrate concentration,non-enzymatic glycosylated proteins, Galectin-3, markers ofinflammation, fibrotic markers, lipid hydroperoxides, thiobarbituricacid reactive substances, malondialdehyde, free F2-IsoPs, dityrosine and8-hydroxy-2′-deoxyguanosine. Examples of markers for inflammationinclude but are not limited to s100B, α1-anti-chymotrypsin, IL-8, IL-1β,macrophage inflammatory protein-1α, macrophage migration inhibitoryfactor, granulocyte-macrophage colony-stimulating factor and TNF-α.Examples of fibrotic markers include but are not limited to matrixmetalloproteinases and hyaluronic acid, pro-inflammatory andpro-fibrotic cytokines, such as tumor necrosis factor-α (TNF-α),transforming growth factor-β, KL-6, SP-A, MMP-7, and CCL-18.

In some embodiments, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the subject haselevated Galectin-3 levels in the blood. In some embodiments, thesubject has elevated levels of fibrotic markers. In some embodiments,the fibrotic markers are in blood. In some embodiments, the fibroticmarkers are in urine. In some embodiments, the subject has an elevatedlevel of a marker of oxidative stress. In some embodiments, the markerof oxidative stress is in blood. In some embodiments, the marker ofoxidative stress is in urine. In some embodiments, the subject has anelevated level of a marker of inflammation. In some embodiments, themarker of inflammation is in blood. In some embodiments, the marker ofinflammation is in urine.

In some embodiments, a method of protecting an organ is provided. Insome embodiments, the method comprises identifying a subject in need ofprotection of an organ and administering a pharmaceutical formulationaccording to any of the embodiments described herein to a subject inneed. In some embodiments, the organ is heart. In some embodiments, theorgan is liver. In some embodiments, the organ is kidney. In someembodiments, the subject has elevated Galectin-3 levels in the blood. Insome embodiments, the subject has elevated levels of fibrotic markers.In some embodiments, the fibrotic markers are in blood. In someembodiments, the fibrotic markers are in urine. In some embodiments, thesubject has an elevated level of a marker of oxidative stress. In someembodiments, the marker of oxidative stress is in blood. In someembodiments, the marker of oxidative stress is in urine. In someembodiments, the subject has an elevated level of a marker ofinflammation. In some embodiments, the marker of inflammation is inblood. In some embodiments, the marker of inflammation is in urine.

In several embodiments, herein, methods are provided for treating,inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has elevatedbiomarkers for oxidative stress. In some embodiments, thetetrahydrocurcumin in the pharmaceutical formulation is not deuterated.In several embodiments, herein, methods are provided for treating,inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has an elevatedbiomarker for Galectin-3. In several embodiments herein, methods areprovided for treating, inhibiting, or ameliorating a disorder in asubject comprising administering a pharmaceutical formulation of any ofthe embodiments described herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has elevatedbiomarkers for oxidative stress. In several embodiments, herein, methodsare provided for treating, inhibiting, or ameliorating a disorder in asubject comprising administering a pharmaceutical formulation of any ofthe embodiments described herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has elevatedfibrotic markers. In several embodiments, herein, methods are providedfor treating, inhibiting, or ameliorating a disorder in a subjectcomprising administering a pharmaceutical formulation of any of theembodiments described herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has elevatedinflammation markers. In several embodiments, herein, methods areprovided for treating, inhibiting, or ameliorating a disorder in asubject comprising administering a pharmaceutical formulation of any ofthe embodiments described herein, comprising a non-deuterated form oftetrahydrocurcumin. In some embodiments, the subject has elevatedinflammation markers. In some embodiments, the pharmaceuticalformulation disclosed herein comprises a non-deuterated form oftetrahydrocurcumin. In some embodiments, the pharmaceutical formulationcomprises deuterated forms of tetrahydrocurcumin, as described inseveral embodiments herein. In some embodiments, the pharmaceuticalformulation disclosed herein comprises a non-deuterated form oftetrahydrocurcumin and a deuterated form of tetrahydrocurcumin, asdescribed in several embodiments herein. In some embodiments, thepharmaceutical formulation further comprises a supplement. In someembodiments, the supplement is curcumin. In some embodiments, thecurcumin is deuterated. In some embodiments, the curcumin isnon-deuterated. In some embodiments, there are non-deuterated anddeuterated forms of curcumin in the pharmaceutical formulation. In someembodiments, the supplement is a terpenoid. In some embodiments, thesupplement is an antioxidant.

In several embodiments, herein, methods are provided for treating,inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a deuterated form of tetrahydrocurcumin. Insome embodiments, the subject has elevated biomarkers for oxidativestress. In several embodiments, herein, methods are provided fortreating, inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a deuterated form of tetrahydrocurcumin. Insome embodiments, the subject has an elevated biomarker for Galectin-3.In several embodiments herein, methods are provided for treating,inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a deuterated form of tetrahydrocurcumin. Insome embodiments, the subject has elevated biomarkers for oxidativestress. In several embodiments, herein, methods are provided fortreating, inhibiting, or ameliorating a disorder in a subject comprisingadministering a pharmaceutical formulation of any of the embodimentsdescribed herein, comprising a deuterated form of tetrahydrocurcumin. Insome embodiments, the subject has elevated fibrotic markers. In severalembodiments, herein, methods are provided for treating, inhibiting, orameliorating a disorder in a subject comprising administering apharmaceutical formulation of any of the embodiments described herein,comprising a deuterated form of tetrahydrocurcumin. In some embodiments,the subject has elevated inflammation markers. In several embodiments,herein, methods are provided for treating, inhibiting, or ameliorating adisorder in a subject comprising administering a pharmaceuticalformulation of any of the embodiments described herein, comprising adeuterated form of tetrahydrocurcumin. In some embodiments, the subjecthas elevated inflammation markers. In some embodiments, thepharmaceutical formulation comprises one or more forms of deuteratedtetrahydrocurcumin. In some embodiments, the pharmaceutical formulationdisclosed herein comprises a non-deuterated form of tetrahydrocurcumin.In some embodiments, the pharmaceutical formulation comprises deuteratedforms of tetrahydrocurcumin, as described in several embodiments herein.In some embodiments, the pharmaceutical formulation disclosed hereincomprises a non-deuterated form of tetrahydrocurcumin and a deuteratedform of tetrahydrocurcumin, as described in several embodiments herein.In some embodiments, the pharmaceutical formulation further comprises asupplement. In some embodiments, the supplement is curcumin. In someembodiments, the curcumin is deuterated. In some embodiments, thesupplement is a terpenoid. In some embodiments, the supplement is anantioxidant.

For example, it has also been shown that tetrahydrocurcumin has ahepatoprotective effect against use with erythromycin estolate (broadspectrum antibiotic) as well as with the use of analgesics.Tetrahydrocurcumin has also been shown to have protective propertiesagainst nephrotoxicity providing protection of oxidative damage to renaltissue. Tetrahydrocurcumin can also have protection after use withanti-malarial drugs, for example chloroquine. Lipid peroxidation causedby disease can also be treated by the anti-oxidative effects oftetrahydrocurcumin.

Liver injury or disease can include but is not limited to alcoholicliver disease, cancer, cirrhosis, cysts, fatty liver disease, fibrosis,hepatitis, jaundice, schlerosing cholangitis, toxic hepatitis, sideeffects stemming from drug use and acetaminophen toxicity. Liverdiseases are a collection of conditions and disorders that can affectthe cells of the liver, the liver structure, the liver tissue and candamage or stop liver functions. In some cases liver injury can be causedby a side effect of prolonged medication use. In some embodiments, amethod of treating, inhibiting, or ameliorating a disorder in a subjectis provided. In some embodiments, the disorder is a liver injury. Insome embodiments, the disorder is a liver disease. In some embodiments,the disorder is a liver injury. In some embodiments, the disorder is afatty liver disease. In some embodiments, the disorder is alcoholicliver disease.

In some embodiments, methods are provided for protecting an organ. Insome embodiments, the method comprises identifying a subject in need ofprotection of an organ and administering the pharmaceutical formulationaccording to any of embodiments described herein to a subject in need.In some embodiments, the pharmaceutical formulation comprisesnon-deuterated forms of tetrahydrocurcumin. In some embodiments, thepharmaceutical formulation comprises deuterated forms oftetrahydrocurcumin, as described in several embodiments herein. In someembodiments, the pharmaceutical formulation comprises non-deuteratedforms of tetrahydrocurcumin and deuterated forms of tetrahydrocurcumin.In some embodiment, the organ is liver. In some embodiments, the subjectsuffers from a liver disorder. In some embodiments, the subject suffersfrom fatty liver disease. In some embodiments, the subject suffers fromalcoholic liver disease. In some embodiments, the subject is human. Insome embodiments, the administering is performed by oral administration.

In some embodiments, the organ is kidney. In some embodiments, thesubject has a kidney disease. In some embodiments, the subject hasdiabetic kidney disease. In some embodiments, he subject has polycystickidney disease. In some embodiments, the subject has hypertension. Insome embodiments, the subject has hypertension with left ventricularhypertrophy. In some embodiments, the subject is human. In someembodiments, the administering is performed by oral administration.

In some embodiments, the organ is heart. In some embodiments, thesubject has heart failure. In some embodiments, the subject has heartdisease.

Fibrosis, as described herein, can refer to the formation of excessfibrous connective tissue in an organ or a tissue that can arise frominjury. Fibrosis is a process that can be similar to scarring which caninclude the process of stimulated cells to produce connective tissue,collagen and glycosaminoglycans. Fibrosis can occur in the lungs, liver,heart, soft tissue of the mediastinum, bone marrow, soft tissue of theretroperitoneum, skin, and intestine. In some embodiments, methods areprovided for treating, inhibiting, or ameliorating a disorder in asubject. In some embodiments, the subject is suffering from fibrosis.

Kidneys are organs that play a regulatory role in vertebrate organisms.They function by filtering waste products in the blood, regulating bloodpressure, electrolyte balance and regulate the red blood cell productionin the body. Lack of kidney function can lead to toxicity, a buildup ofwaste products that can cause weakness, lethargy and confusion. Theinability to remove toxins and potassium from the bloodstream can leadto abnormal heart rhythms and sudden death.

Kidney damage that can lead to kidney failure can be caused by manyfactors. Nephropathy (kidney disease), and Nephritis (inflammatorykidney disease) can be caused by, for example, the use of long termanalgesics, a decreased function of xanthine oxidase, polycystic diseaseof the kidneys, chemotherapy agents, and autoimmune diseases. Kidneydisease can include but is not limited to diabetic kidney disease, andpolycystic kidney disease. In some embodiments, a method of treating,inhibiting, or ameliorating a disorder in a subject is provided. In someembodiments, the disorder is a kidney disease. In some embodiments, thedisorder is diabetic kidney disease. In some embodiments, the disorderis polycystic kidney disease. In some embodiments, methods are providedfor protecting an organ. In some embodiment, the organ is kidney.

“Heart failure” can also be referred to as chronic heart failure, and isthe inability of the heart to pump sufficiently to maintain the bloodflow to meet the body's needs. Causes of heart failure can include butit is not limited to coronary artery disease, a previous myocardialinfarction, myocardial infarction (heart attack), high blood pressure,atrial fibrillation, valvular heart disease, excess alcohol use,infection, and cardiomyopathy. In some embodiments of the treatmentsprovided herein, the subject has heart failure. In some embodiments thesubject has coronary artery disease, a previous myocardial infarction,myocardial infarction (heart attack), high blood pressure, atrialfibrillation, valvular heart disease, excess alcohol use, infection or acardiomyopathy. Several embodiments herein relate to the treatment andprevention of heart failure.

Additional Embodiments

The following examples are intended to illustrate, but not to limit, theinvention in any manner, shape, or form, either explicitly orimplicitly. While they are typical of those that might be used, otherprocedures, methodologies, or techniques known to those skilled in theart may alternatively be used.

Diagnosis of Liver Damage

In order to determine a subject in need experiments are performed toexamine damage by conducting analysis to quantitate levels of Aspartatetransaminase (AST) and Alanine transaminase, alkaline phosphatase (ALP),and bilirubin in a subject.

Effect of Pharmaceutical Formulations Comprising Both Tetrahydrocurcuminand Curcumin.

In order to test the effects of tetrahydrocurcumin alone, curcuminalone, and curcumin in combination with tetrahydrocurcumin, diabeticrats and control rats were given oral administration of pharmaceuticalformulations comprising of tetrahydrocurcumin alone, curcumin alone, andcurcumin in combination with tetrahydrocurcumin. Oral administration oftetrahydrocurcumin was given at 80 mg/kg body weight to 12 diabetic ratsand 12 control rats for 45 days. Oral administration of curcumin wasgiven at 100 mg/kg body weight to 12 diabetic rats and 12 control ratsfor 45 days. Additionally oral administration of a combination oftetrahydrocurcumin (80 mg/kg body weight) and curcumin (100 mg/kg bodyweight) were given to 12 diabetic rats and 12 control rats for 45 days.After 45 days, the levels of blood glucose, total protein, albumin,globulin and albumin/globulin ratios were examined.

Deuterated Tetrahydrocurcumin for Treatment.

In order to examine the efficacy of tetrahydrocurcumin in the deuteratedform, oral administration of deuterated tetrahydrocurcumin was orallyadministered to 12 diabetic rats and 12 control rats for 45 days (40mg/kg body weight). Additionally oral administration of deuteratedtetrahydrocurcumin was orally administered to 12 diabetic rats and 12control rats for 45 days with an increased amount of tetrahydrocurcumin(80 mg/kg body weight) As a control, non-deuterated form oftetrahydrocurcumin was orally administered to 12 diabetic rats and 12control rats for 45 days (40 mg/kg body weight) and non-deuterated formof tetrahydrocurcumin was orally administered to 12 diabetic rats and 12control rats with an increased concentration of non-deuteratedtetrahydrocurcumin (80 mg/kg body weight. In order to examine theefficacy of the drug, the different amounts of the tetrahydrocurcuminwere tested in order to examine the effects of the drug concentration totest the ability of the deuterated tetrahydrocurcumin to remain withinthe system. After 45 days, the levels of blood glucose, total protein,albumin, globulin and albumin/globulin ratios were examined.

Dietary Tetrahydrocurcumin Supplementation Slows Progression of KidneyDisease and Decreases Proteinuria in 5/6 Nephrectomy Rats.

Curcumin, a diarylheptanoid present in turmeric, has shown promise as anantioxidant and anti-inflammatory agent in animal models of kidneyfailure. However, as curcumin is composed of several phenols and some ofthese compounds may exert paradoxical pro-inflammatory effects, themajor metabolite of curcumin, tetrahydrocurcumin (THC) was examined inrats with chronic kidney disease (CKD) for THC effects.

For induction of CKD via nephron mass reduction, Sprague-Dawley ratsunderwent partial left nephrectomy followed by total right nephrectomyone week later. CKD rats were then randomized to 1% THC diet withpolyenylphosphatidylcholine (PPC, 3 g/1000 kcal) vs. regular chow. THChas poor bioavailability, and co-administration with a lipid carriersuch as PPC has previously been shown to increase plasma levels 5-fold.Tail blood pressure measurement and 24-hour urine collection were donewithin a week of study termination. After 9 weeks on special diet, bloodand kidneys were collected for biochemical and histologic analyses.

The experimental groups included healthy controls, CTL n=5, non-treatedCKD, n=6 and CKD/THC n=6. Findings are summarized in Table 1. At time ofrandomization to regular chow vs. THC diet, average blood urea nitrogen(BUN) was similar between the CKD groups (63.5+10.5 vs. 66+16.5 mg/dL).BUN was significantly lower in the CKD/THC group at termination of thestudy, by about 40% compared to the non-treated CKD group. Proteinuriawas significantly decreased by almost 50% in CKD/THC compared tonon-treated CKD animals. The CKD/THC group showed significantamelioration of hypertension, and a trend for decreased cardiachypertrophy as measured by normalized heart weight (P=0.06). Imagequantitative analysis of Trichrome stained slides of kidney tissueshowed a trend for decreased renal fibrosis in CKD/THC animals (P=0.1).Plasma C-reactive protein was not different between CKD groups (P=0.9),suggesting that non-anti-inflammatory mechanisms were at play.

TABLE 1 Summary of Results of blood tests following induced CDK. P valuecomparing CTL CKD CKD/THC CKD Measured parameter (n = 5) (n = 6) (n = 6)groups Systolic blood pressure 100.2 ± 6.7  140 ± 6.4  116.5 ± 11.1 <0.01 (mmHg) Diastolic blood pressure 79.6 ± 7.7  93.7 ± 9.3  75.8 ±12.8 <0.05 (mmHg) Body weight at termination  280 ± 19.1 259.8 ± 12.9 256.8 ± 7.2  0.6 (g) Heart wet weight normalized 3.54 ± 0.3  4.61 ± 0.5 3.89 ± 0.61 0.06 to body weight (g/kg) BUN at termination (mg/dL) 19.4 ±2   87.1 ± 32.9 52.1 ± 19.1 <0.05 Plasma creatinine (mg/dL) 0.46 ± 0.151.37 ± 0.47 1.04 ± 0.22 0.2 Plasma C-reactive protein 1.55 ± 0.81 2.77 ±1.2  2.71 ± 0.5  0.9 (mg/ml) Urine protein/creatinine 2.15 ± 2.34 88.53± 30.94 47.91 ± 15.42 <0.05 (mg/g) Kidney fibrosis from   1 ± 0.17 1.37± 0.03 1.16 ± 0.24 0.1 Trichrome stained slides: relative % area

As indicated by the experiments, a 1% tetrahydrocurcumin diet decreasedthe rate of CKD progression in 5/6 nephrectomy rats. There was also afinding that there was significant decrease in proteinuria andhypertension, and a trend for decreased renal fibrosis.

Tetrahydrocurcumin Treatment in Rats.

Rats were induced to have chronic kidney disease via nephron massreduction, Sprague-Dawley rats underwent partial left nephrectomyfollowed by total right nephrectomy one week later. CKD rats were thenrandomized to 1% THC diet with polyenylphosphatidylcholine (PPC, 3g/1000 kcal) vs. regular chow. The rats were then administered a dose ofBuprenex, a narcotic, that can cause kidney damage. As shown in Table 2,are the weights of the test rats during the surgical procedure, beforeand after the administration of Buprenex.

After 24 hours the rats were analyzed for proteinuria, Galectin-3, andC-reactive protein. Galectin-3 is a marker for cardiac fibrosis, andC-reactive protein is correlated with inflammation. Furthermore, a bloodurea nitrogen test (BUN) was carried out with a creatinine andcreatinine clearance blood test to evaluate the kidney functions and tolook for nephrotoxicity. As shown in Table 3, are the results of theblood tests on the rats following the induced kidney disease.

TABLE 2 Weights of rats following nephrectomy and treatment withBuprenex Surgery #2 Right total nephrectomy Weights checked week WtBuprenex Doses of Post-op day (g) Date (g) mL Buprenex #1 Notes Jan. 28,2015 Feb. 12, 2015 Jan. 20, 2015 239 0.2 229 248 0.2 All 8 rats # 2 Alittle 233 received 2 scruffy doses: start of surgery and at 4 pm 2280.2 225 234 0.2 No Buprenex 220 241 0.2 given to any #5: No 243 Rats1-16 rat right (except 5 kidney and 13) found --> Feb. 3, 2015 rateuthanized, R kidney had adhesions to liver 250 0.2 236 randomized toCKD treatment groups 251 0.2 254 235 0.2 231 Jan. 28, 2015 Jan. 22, 2015236 0.2 228 251 0.2 240 243 0.2 235 240 0.2 2 doses 230 Buprenex 238 0.2Dose at No additional 1st 230 start of Buprenex to incision surgery anyrats from and at surgery #1 4 pm re-stapled; resulted in some bleeding248 0.2 Rats 14- 238 16 kept in separate cages because 240 0.2 #14 and237 #16 with less well- healed 1st incisions Feb. 3, 2015 257 0.2 236270 0.25 255 255 0.2 251 243 0.2 All 8 rats 243 received 2 doses: startof surgery and at 4 pm 245 0.2 243 Rats randomize to special diets Feb.12, 2015 254 0.2 267 224 0.2 230 248 0.2 240 Feb. 5, 2015 250 0.2 240236 0.2 227 246 0.2 240 275 0.25 270 256 0.2 250 258 0.2 250 266 0.2 256223 0.15 188

TABLE 3 Blood test results of rats following induced kidney disease. 24hr total Terminal Terminal proteinuria Uprot/Cr Cardiac BUN Cr CrCLGalectin-3 CRP Rat# (mg) ratio mg/g puncture mg/dL mg/dL ml/min*kg ng/mlmg/ml 561.8 88.04 73.8 0.92 2.01 694.64 4.06 9 15 655.1 52.30 49.8 0.963.30 483.86 2.77 20 605.8 58.89 51.4 0.98 2.74 322.44 2.92 23 307.1102.54 117.2 1.82 0.44 380.11 3.55 25 1066.0 137.39 121.4 1.64 1.22644.10 0.56 31 782.6 92.01 109.1 1.92 1.23 326.41 2.78 32 8 638.5 63.1844.9 0.76 3.71 285.96 2.53 10 11 612.7 64.86 60.3 1.28 1.90 450.48 3.2212 355.6 30.56 80.6 1.25 2.56 436.37 2.15 14 537.7 46.32 107.7 1.48 2.27768.79 4.38 18 — — 69.9 1.19 — 273.14 2.70 19 613.8 43.50 hemolyzed 32.11.13 3.46 — 3.43 21 410.1 37.43 hemolyzed 32.6 1.01 2.91 — 2.36 22 — —201.8 2.30 — 182.38 1.19 27 — — hemolyzed 62.3 0.81 — — 2.57 1 690.570.69 102.2 1.29 1.96 363.12 3.73 2 616.2 93.95 hemolyzed 90.3 1.37 1.38— 1.24 7 — — 74.7 0.93 — 277.39 1.92 16 844.1 81.25 69.4 1.38 2.20322.99 2.70 17 — — 50.4 1.09 — 563.52 1.98 24 244.0 27.81 30.4 0.82 2.91707.01 2.26 26 817.1 108.13 hemolyzed 97.8 1.12 2.00 — 0.89 28 710.168.29 hemolyzed 75.7 1.11 2.49 — 0.79 29 — — 42.2 1.08 — 338.09 3.85 30— — 36.2 1.22 — 130.20 3.75 33 19.1 1.66 19.4 0.43 6.05 244.33 2.93 346.5 0.67 22.4 0.71 3.25 290.48 0.97 35 266.2 28.31 26.5 0.42 5.39 498.793.67 36 9.4 1.05 17.8 0.44 5.23 632.34 1.17 37 8.5 1.08 19.8 0.31 6.66520.15 1.65 38 46.8 6.28 17.4 0.42 4.67 480.68 1.05

After inducing chronic kidney disease, the rats were then treated with apharmaceutical formulation comprising tetrahydrocurcumin, or with apharmaceutical formulation that had both tetrahydrocurcumin andcurcumin. The control group consisted of five rats, (rat numbers 33-38),the rats with CKD (rat number 4, 15, 20, 23, 25, 31), rats with chronickidney disease treated with tetrahydrocurcumin (rat number 8, 11, 12,14, 19, 21, 18 and 27) and rats treated with a combination oftetrahydrocurcumin and curcumin (rat number 1, 2, 16, 24, 28, 7, 17, 29and 30). The results of the change in their blood tests are shown inTables 4 -11. The measurements for the average BUN, blood pressure, bodyweight, delta BUN, Hgb, and Heart weight/body weight for the four groupsare shown in FIGS. 2A-2G. The blood pressures were also measured for thegroups of rats, and the study indicated a positive impact oftetrahydrocurcumin on hypertension, as well as development of cardiachypertrophy.

The blood urea nitrogen test (BUN) is primarily used with the creatininetest to evaluate kidney function and to help diagnose kidney disease. Asshown in FIG. 2, panel A and B, there is a decrease in the blood ureanitrogen following treatment with either tetrahydrocurcumin alone orwith curcumin (groups 3 and 4), in comparison to the rats with inducedkidney disease (group 2). Furthermore, the blood pressure decreased inthe treated rats in comparison to the rats with induced kidney disease(group 2) (FIG. 2 panel F and panel G). Therefore the pharmaceuticalformulations comprising tetrahydrocurcumin with or without curcumin canbe used to treat hypertension. Accordingly, there was no noticeablechange in body weight, hemoglobin levels, and heart weight/body weightratios as seen in FIG. 2 panels C, D and E.

TABLE 4 Change in BUN and heart/body weight following treatment withpharmaceutical formulations comprising tetrahydrocurcumin or bothtetrahydrocurcumin and curcumin. Terminal Termination Term HeartRandomization BUN Change body Hgb Heart wt/body wt Group Rat# BUN mg/dLmg/dL in BUN weight (g) g/dL wt (g) (g/kg) 1: CTL 33 19.4 308 13.8 1.0703.47 34 22.4 290 13.8 0.977 3.37 #35 out 36 17.8 275 14.6 0.875 3.18 3719.8 265 14.1 0.995 3.75 38 17.4 262 13.6 1.028 3.92 AVE 19.4 280 13.980.989 3.54 S.D. 2.0 19.1 0.4 0.073 0.30 2: CKD  4 69.5 73.8 4.3 240 14.50.956 3.98 15 51.9 49.8 −2.1 274 13 1.207 4.41 20 63.7 51.4 −12.3 26614.7 1.185 4.45 23 50.2 117.2 67.0 259 13.1 1.219 4.71 25 76.7 121.444.7 270 14.8 1.243 4.60 31 68.7 109.1 40.4 250 12.3 1.377 5.51 AVE 63.587.1 23.7 259.8 13.7 1.198 4.61 S.D. 10.5 32.9 31.4 12.9 1.1 0.137 0.503:  8 58.5 44.9 −13.6 250 12.7 1.169 4.68 CKD/THC 11 66.5 60.3 −6.2 26913.7 0.972 3.61 #22 out 12 96.5 80.6 −15.9 254 13 1.165 4.59 14 76.1107.7 31.6 239 11.4 1.035 4.33 19 60.8 32.1 −28.7 250 13.1 0.854 3.42 2147.3 32.6 −14.7 258 12 0.830 3.22 18 66.5 69.9 3.4 272 14 1.530 5.63 2766.6 62.3 −4.3 260 11.8 0.989 3.80 AVE 67.4 61.3 −6.0 256.5 12.7 1.0684.16 S.D. 14.4 25.5 17.9 10.7 0.9 0.224 0.80 4:  1 63.3 102.2 38.9 26814.6 1.057 3.94 CKD/THC/ curcumin  2 59.5 90.3 30.8 240 13.6 0.899 3.7516 95.4 69.4 −26.0 238 14 0.785 3.30 #26 out 24 60.9 30.4 −30.5 254 12.30.985 3.88 28 52 75.7 23.7 261 12.7 1.075 4.12  7 80.7 74.7 −6.0 26512.9 1.029 3.88 17 72.3 50.4 −21.9 250 13.7 1.135 4.54 29 63.7 42.2−21.5 279 13.8 1.057 3.79 30 64.4 36.2 −28.2 266 13.5 1.016 3.82 AVE68.0 63.5 4.5 257.9 13.5 1.004 3.89 S.D. 13.1 25.0 27.9 13.5 0.7 0.1050.33 ANOVA no no no no yes for 2, 4 P < 0.05 between CKD gps

TABLE 5 Measurements of C reactive protein, proteinuria, and Urineprotein/creatinine following treatments for chronic kidney disease.Systolic 24 hr total tail BP Diastolic Terminal proteinuria Uprot/RPGroup Rat# mmHg tail BP sCr mg/dL (mg) mg/ml 1: CTL 33 97 74 0.43 19.152.93 34 99 74 0.71 6.45 0.97 #35 out 36 101 82 0.44 9.43 1.17 37 93 760.31 8.45 1.65 38 111 92 0.42 46.75 1.05 AVE 100.2 79.6 0.46 18.05 1.55S.D. 6.7 7.7 0.15 16.78 0.81 2: CKD  4 146 98 0.92 561.77 4.06 15 139108 0.96 655.08 2.77 20 132 81 0.98 605.77 2.92 23 141 95 1.82 307.103.55 25 148 87 1.64 1065.96 0.56 31 134 93 1.92 782.57 2.78 AVE 140 93.71.37 663.04 2.77 S.D. 6.4 9.3 0.47 251.76 1.20 3:  8 132 95 0.76 638.502.53 CKD/THC 11 103 69 1.28 612.75 3.22 #22 out 12 124 60 1.25 355.612.15 14 116 78 1.48 537.69 4.38 19 113 81 1.13 613.82 3.43 21 106 671.01 410.08 2.36 18 124 77 1.19 2.70 27 121 83 0.81 2.57 AVE 117.4 76.31.11 528.07 2.92 S.D. 9.8 10.9 0.24 118.72 0.73 4:  1 121 92 1.29 690.513.73 CKD/THC/ curcumin  2 114 88 1.37 616.18 1.24 16 112 90 1.38 844.122.70 #26 out 24 97 57 0.82 244.03 2.26 28 125 84 1.11 710.12 0.79  7 10981 0.93 1.92 17 107 81 1.09 1.98 29 101 79 1.08 3.85 30 96 74 1.22 3.75AVE 109.1 80.7 1.14 620.99 2.15 S.D. 10.1 10.5 0.19 226.21 1.17 ANOVAyes yes for 2, 3 P < 0.05 between CKD gps

TABLE 6 Measurements of Terminal Cr, CrCL (Creatinine Clearance), CRP (Creactive protein) and Galectin-3 following treatments for chronic kidneydisease in rats. Terminal Cr CrCL Galectin-3 CRP Group Rat# mg/dLml/min*kg ng/ml mg/ml 1: CTL 33 0.43 6.05 244.33 2.93 34 0.71 3.25290.48 0.97 #35 out 36 0.44 5.23 632.34 1.17 37 0.31 6.66 520.15 1.65 380.42 4.67 480.68 1.05 AVE 0.46 5.17 433.60 1.55 S.D. 0.15 1.32 162.410.81 2: CKD  4 0.92 2.01 694.64 4.06 15 0.96 3.30 483.86 2.77 20 0.982.74 322.44 2.92 23 1.82 0.44 380.11 3.55 25 1.64 1.22 644.10 0.56 311.92 1.23 326.41 2.78 AVE 1.37 1.82 475.26 2.77 S.D. 0.47 1.07 162.031.20 3:  8 0.76 3.71 285.96 2.53 CKD/THC 11 1.28 1.90 450.48 3.22 #22out 12 1.25 2.56 436.37 2.15 14 1.48 2.27 768.79 4.38 19 1.13 3.46 3.4321 1.01 2.91 2.36 18 1.19 273.14 2.70 27 0.81 2.57 AVE 1.11 2.80 442.952.92 S.D. 0.24 0.70 199.84 0.73 4:  1 1.29 1.96 363.12 3.73 CKD/THC/curcumin  2 1.37 1.38 — 1.24 16 1.38 2.20 322.99 2.70 #26 out 24 0.822.91 707.01 2.26 28 1.11 2.49 — 0.79  7 0.93 277.39 1.92 17 1.09 563.521.98 29 1.08 338.09 3.85 30 1.22 130.20 3.75 AVE 1.20 2.19 464.37 2.15S.D. 0.23 0.57 211.08 1.17 ANOVA P < 0.05 between CKD gps

TABLE 7 Terminal Bun and Terminal Cr measurements in control rats, ratswith induced chronic kidney disease (CKD), rats treated withtetrahydrocurcumin after CDK, and rats treated withtetrahydrocurcumin/curcumin after CDK. Terminal Terminal BUN Cr Rat#mg/dL mg/dL Gp 1 CTL 33 19.4 0.4 34 22.4 0.7 35 26.5 0.4 36 17.8 0.4 3719.8 0.3 38 17.4 0.4 Gp 2 CKD 4 73.8 0.9 15 49.8 1.0 20 51.4 1.0 23117.2 1.8 25 121.4 1.6 31 109.1 1.9 Gp 3 CKD/thc 8 44.9 0.8 11 60.3 1.312 80.6 1.2 14 107.7 1.5 18 69.9 1.2 19 32.1 1.1 21 32.6 1.0 22 201.82.3 27 62.3 0.8 Gp 4 thc/ 1 102.2 1.3 curcumin 2 90.3 1.4 7 74.7 0.9 1669.4 1.4 17 50.4 1.1 24 30.4 0.8 26 97.8 1.1 28 75.7 1.1 29 42.2 1.1 3036.2 1.2

TABLE 8 Four groups of rats were subjected to blood tests to examinechanges in BUN weight and Hgb following treatment withtetrahydrocurcumin or a combination of tetrahydrocurcumin with curcumin.The groups were control, rats with induced CKD, rats treated withtetrahydrocurcumin following induced CKD, and rats treated withtetrahydrocurcumin/curcumin following induced CKD. Heart TerminalTermination Term wt/body Randomization BUN Change in body weight HgbHeart wt Rat# BUN mg/dL mg/dL BUN (g) g/dL wt (g) (g/kg) 33 19.4 30813.8 1.070 3.47 34 22.4 290 13.8 0.977 3.37 36 17.8 275 14.6 0.875 3.1837 19.8 265 14.1 0.995 3.75 38 17.4 262 13.6 1.028 3.92 AVE 19.4 28013.98 0.989 3.54 S.D. 2.0 19.1 0.4 0.073 0.30  4 69.5 73.8 4.3 240 14.50.956 3.98 15 51.9 49.8 −2.1 274 13 1.207 4.41 20 63.7 51.4 −12.3 26614.7 1.185 4.45 23 50.2 117.2 67.0 259 13.1 1.219 4.71 25 76.7 121.444.7 270 14.8 1.243 4.60 31 68.7 109.1 40.4 250 12.3 1.377 5.51 AVE 63.587.1 23.7 259.8 13.7 1.198 4.61 S.D. 10.5 32.9 31.4 12.9 1.1 0.137 0.50 8 58.5 44.9 −13.6 250 12.7 1.169 4.68 11 66.5 60.3 −6.2 269 13.7 0.9723.61 12 96.5 80.6 −15.9 254 13 1.165 4.59 19 60.8 32.1 −28.7 250 13.10.854 3.42 21 47.3 32.6 −14.7 258 12 0.830 3.22 27 66.6 62.3 −4.3 26011.8 0.989 3.80 AVE 66.0 52.1 −13.9 256.8 12.7 0.997 3.89 S.D. 16.5 19.18.7 7.2 0.7 0.146 0.61 ANOVA Y Y Y P < 0.05? P-value <0.01 n.s. <0.01 Gp1&2 P-value <0.05 ttest <0.05 n.s. n.s. 0.06 Gp 2&3 P-value n.s. <0.05n.s. 0.5 Gp 1&3

TABLE 9 Three groups of rats were subjected to blood tests to examinechanges in uprot/CR, CrCL, Galectin-3 and CRP measurements followingtreatment with tetrahydrocurcumin or a combination of tetrahydrocurcuminwith curcumin. The groups were control, rats with induced CKD, and ratstreated with tetrahydrocurcumin/curcumin following induced CKD. Terminal24 hr total Diastolic sCr proteinuria Uprot/Cr CrCL Galectin-3 CRP GroupRat# tail BP mg/dL (mg) ratio mg/g ml/min*kg ng/ml mg/ml 1: CTL 33 740.43 19.15 1.66 6.05 244.33 2.93 34 74 0.71 6.45 0.67 3.25 290.48 0.97#35 out 36 82 0.44 9.43 1.05 5.23 632.34 1   21 67 1.01 410.08 37.432.91 hemolyzed 2.36 27 83 0.81 hemolyzed 2.57 AVE 75.8 1.04 526.15 47.912.91 390.94 2.71 S.D. 12.8 0.22 132.63 15.42 0.72  91.19 0.50 ANOVA Y YY Y Y P = 0.07 P < 0.05? Tukey P-value n.s. <0.01 <0.01 <0.01 <0.01 0.09posthoc test Gp 1&2 P-value <0.05 n.s. 0.2 n.s. <0.05 n.s. 0.9  Gp 2&3P-value n.s. <0.05 <0.01 <0.05 <0.05 0.12 Gp 1&3

TABLE 10 The three groups of rats of Table 7 were then killed andexamined for fibrosis of the kidney. The table presents the relativepercent area of fibrosis in the kidneys of the three groups. The groupswere control, rats with induced CKD, and rats treated withtetrahydrocurcumin/curcumin following induced CKD. Kidney slidesRelative % Trichrome stain area fibrosis Gp 1 CTL 0.809435 1.182758 Ave1 1.050894 SD 0.1674 1.197113 0.886911 0.872889 Gp 2 CKD 1.3821361.374501 Ave 1.3719 1.422038 SD 0.0315 1.337959 1.337959 1.376647 Gp 3CKD/THC 1.395675 1.32091 Ave 1.1551 1.345161 SD 0.2435 0.895843 1.1460170.826866

The results of the treatment of the rats show a positive impact of THCon hypertension, as well as development of cardiac hypertrophy, as seenin the effects for the diastolic and systolic blood pressure followingtreatment with tetrahydrocurcumin with or without the addition ofcurcumin (Tables 1, 5 and 9).

TABLE 11 Measurement of nephrosis in the kidneys of the four groups ofrats (Control, induced CKD, treatment of tetrahydrocurcumin followinginduced CKD and treatment of tetrahydrocurcumin/curcumin followinginduced CKD). % area Group 1 CTL Sample 1 1 1228794 0.164 16.409 21228793 0.23  23.042 3 1228796 0.13  12.971 average 17.474 Sample 2 11228798 0.296 29.641 2 1228797 0.424 42.357 3 1228796 0.282 28.157average 33.385 Sample3 1 1228742 0.655 65.538 2 1228792 0.275 27.505 31228794 0.247 24.726 average 39.25633 Sample4 1 1228798 0.201 20.091 21228800 0.156 15.635 3 1228800 0.193 19.348 Average 18.358 Sample5 11228800 0.533 53.268 2 1228765 0.543 54.287 3 1228779 0.634 63.369Average 56.97467 Sample6 1 1228798 0.228 22.761 2 1228800 0.276 27.583 31228800 0.243 24.289 Average 24.87767 Group 2 CKD Sample 1 1 12287730.339 33.922 2 1228776 0.49  48.959 3 1228785 0.413 41.258 average41.37967 Sample2 1 1228798 0.521 52.065 2 1228711 0.548 54.831 3 12287150.684 68.382 Average 58.426 Sample3 1 1228774 0.816 81.636 2 12286620.781 78.07 3 1228800 0.787 78.746 Average 79.484 Sample4 1 12287990.699 69.937 2 1228789 0.766 76.573 3 1228715 0.684 68.382 Average71.63067 Sample5 1 1228768 0.648 64.842 2 1228792 0.555 55.475 3 12287900.532 53.175 Average 57.83067 Sample6 1 1228780 0.758 75.769 2 12287890.725 72.53 3 1228798 0.754 75.45 Average 74.583 Group 3 CKD + THCSample 1 1 1228765 0.719 71.895 2 1228757 0.714 71.431 3 1228757 0.73773.721 Average 72.349 Sample2 1 1228774 0.617 61.721 2 1228776 0.66866.83 3 1228752 0.696 69.556 Average 66.03567 Sample3 1 1228792 0.79 79.041 2 1228766 0.601 60.075 3 1228788 0.695 69.458 Average 69.52467Sample4 1 1228775 0.491 49.106 2 1228797 0.556 55.623 3 1228798 0.20720.679 Average 41.80267 Sample5 1 1228739 0.321 32.058 2 1228781 0.41841.754 3 1228799 0.166 16.589 Average 30.13367 Sample6 1 1228791 0.39939.869 2 1228791 0.177 17.667 3 1228799 0.365 36.541 Average 31.359Group 4 CKD + THC/curcumin Sample 1 1 1228755 0.55  55.01 2 12287750.447 44.687 3 1228730 0.409 40.908 Average 46.86833 Sample2 1 12285990.503 50.288 2 1228793 0.539 53.913 3 1228759 0.53  52.979 Average52.39333 Sample3 1 1228770 0.667 66.679 2 1228772 0.557 55.669 3 12287470.49  48.983 Average 57.11033 Sample4 1 1228743 0.541 54.148 2 12287230.615 61.512 3 1228780 0.557 55.733 Average 57.131 Sample5 1 12287290.685 68.474 2 1228799 0.502 50.178 3 1228745 0.637 63.737 Average60.79633 Sample6 1 1228761 0.706 70.589 2 1228752 0.401 40.136 3 12287610.725 72.516 Average 61.08033

More Embodiments

In some embodiments, a pharmaceutical formulation is provided. In someembodiments, the pharmaceutical formulation comprises a non-deuteratedform of tetrahydrocurcumin and a pharmaceutical vehicle. In someembodiments, the pharmaceutical formulation further comprises a firstlipid. In some embodiments, the first lipid is a phospholipid. In someembodiments, the first lipid is polyenylphosphatidylcholine. In someembodiments, the pharmaceutical formulation comprises at least 5% of thefirst lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the first lipid by weight. Insome embodiments, the pharmaceutical formulation further comprises asecond lipid. In some embodiments, the pharmaceutical formulationcomprises at least 5% of the second lipid by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the second lipid by weight. In some embodiments, the second lipid isomega-3. In some embodiments, the second lipid is omega-3 from fish orflaxseed. In some embodiments, the pharmaceutical formulation furthercomprises an antioxidant. In some embodiments, the pharmaceuticalformulation comprises at least 5% of antioxidant by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the antioxidant by weight. In some embodiments, the antioxidant isVitamin E. In some embodiments, the antioxidant is Vitamin C. In someembodiments, the antioxidant is alpha lipoic acid. In some embodiments,the pharmaceutical formulation further comprises curcumin. In someembodiments, the pharmaceutical formulation further comprises aterpenoid. In some embodiments, the pharmaceutical formulation furthercomprises cysteamine. In some embodiments, the pharmaceuticalformulation further comprises pantethine. In some embodiments, thecurcumin is deuterated. In some embodiments, the vehicle is a lipophilicsolvent, fatty oil, organic oil, or liposome. In some embodiments, thepharmaceutical formulation further comprises an excipient. In someembodiments, the excipient is a sugar, lactose, sucrose, mannitol,sorbitol, cellulose preparations of maize starch, wheat starch, ricestarch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP). In some embodiments, the pharmaceuticalformulation further comprises baicalin.

In some embodiments, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the methodcomprises administering the pharmaceutical formulation of any of theembodiments described herein to the subject. In some embodiments, thepharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin and a pharmaceutical vehicle. In some embodiments,the pharmaceutical formulation further comprises a first lipid. In someembodiments, the first lipid is a phospholipid. In some embodiments, thefirst lipid is polyenylphosphatidylcholine. In some embodiments, thepharmaceutical formulation comprises at least 5% of the first lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the first lipid by weight. In some embodiments, thepharmaceutical formulation further comprises a second lipid. In someembodiments, the pharmaceutical formulation comprises at least 5% of thesecond lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the second lipid by weight. Insome embodiments, the second lipid is omega-3. In some embodiments, thesecond lipid is omega-3 from fish or flaxseed. In some embodiments, thepharmaceutical formulation further comprises an antioxidant. In someembodiments, the pharmaceutical formulation comprises at least 5% ofantioxidant by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the antioxidant by weight. Insome embodiments, the antioxidant is Vitamin E. In some embodiments, theantioxidant is Vitamin C. In some embodiments, the antioxidant is alphalipoic acid. In some embodiments, the pharmaceutical formulation furthercomprises curcumin. In some embodiments, the pharmaceutical formulationfurther comprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thevehicle is a lipophilic solvent, fatty oil, organic oil, or liposome. Insome embodiments, the pharmaceutical formulation further comprises anexcipient. In some embodiments, the excipient is a sugar, lactose,sucrose, mannitol, sorbitol, cellulose preparations of maize starch,wheat starch, rice starch, potato starch, gelatin, gum tragacanth,methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In someembodiments, the pharmaceutical formulation further comprises baicalin.In some embodiments, the disorder is a liver disorder. In someembodiments, the disorder is a fatty liver disease. In some embodiments,the disorder is alcoholic liver disease. In some embodiments, thedisorder is a kidney disease. In some embodiments, the disorder isdiabetic kidney disease. In some embodiments, the disorder is polycystickidney disease. In some embodiments, the disorder is hypertension. Insome embodiments, the disorder is hypertension with left ventricularhypertrophy. In some embodiments, the disorder is diabetes. In someembodiments, the disorder is diabetes with hyperlipidemia. In someembodiments, the subject has elevated Galectin-3 levels in the bloodand/or urine. In some embodiments, the subject has elevated levels offibrotic markers. In some embodiments, the fibrotic markers are inblood. In some embodiments, the fibrotic markers are in urine. In someembodiments, the subject has an elevated level of a marker of oxidativestress. In some embodiments, the marker of oxidative stress is in blood.In some embodiments, the marker of oxidative stress is in urine. In someembodiments, the subject has an elevated level of a marker ofinflammation. In some embodiments, the marker of inflammation is inblood. In some embodiments, the marker of inflammation is in urine. Insome embodiments, the pharmaceutical formulation is administered to thesubject by oral administration. In some embodiments, the administeringis performed by intravenous administration. In some embodiments, thesubject is human. In some embodiments, the subject is taking analgesics.In some embodiments, the subject is under treatment with one or moreanti-malarial drugs. In some embodiments, the subject has heart failure.

In some embodiments, a method of protecting an organ is provided. Insome embodiments, the method comprises identifying a subject in need ofprotection of an organ and administering the pharmaceutical formulationof any of the embodiments described herein to a subject in need. In someembodiments, the pharmaceutical formulation comprises a non-deuteratedform of tetrahydrocurcumin and a pharmaceutical vehicle. In someembodiments, the pharmaceutical formulation further comprises a firstlipid. In some embodiments, the first lipid is a phospholipid. In someembodiments, the first lipid is polyenylphosphatidylcholine. In someembodiments, the pharmaceutical formulation comprises at least 5% of thefirst lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the first lipid by weight. Insome embodiments, the pharmaceutical formulation further comprises asecond lipid. In some embodiments, the pharmaceutical formulationcomprises at least 5% of the second lipid by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the second lipid by weight. In some embodiments, the second lipid isomega-3. In some embodiments, the second lipid is omega-3 from fish orflaxseed. In some embodiments, the pharmaceutical formulation furthercomprises an antioxidant. In some embodiments, the pharmaceuticalformulation comprises at least 5% of antioxidant by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the antioxidant by weight. In some embodiments, the antioxidant isVitamin E. In some embodiments, the antioxidant is Vitamin C. In someembodiments, the antioxidant is alpha lipoic acid. In some embodiments,the pharmaceutical formulation further comprises curcumin. In someembodiments, the pharmaceutical formulation further comprises aterpenoid. In some embodiments, the pharmaceutical formulation furthercomprises cysteamine. In some embodiments, the pharmaceuticalformulation further comprises pantethine. In some embodiments, thecurcumin is deuterated. In some embodiments, the vehicle is a lipophilicsolvent, fatty oil, organic oil, or liposome. In some embodiments, thepharmaceutical formulation further comprises an excipient. In someembodiments, the excipient is a sugar, lactose, sucrose, mannitol,sorbitol, cellulose preparations of maize starch, wheat starch, ricestarch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP). In some embodiments, the pharmaceuticalformulation further comprises baicalin. In some embodiments, the organis kidney. In some embodiments, the organ is liver. In some embodiments,the organ is heart. In some embodiments, the subject is human. In someembodiments, the administering is performed by oral administration. Insome embodiments, the administering is performed by intravenousadministration. In some embodiments, the subject has a liver disorder.In some embodiments, the subject has a fatty liver disease. In someembodiments, the subject has alcoholic liver disease. In someembodiments, the subject has a kidney disease. In some embodiments, thesubject has diabetic kidney disease. In some embodiments, the subjecthas polycystic kidney disease. In some embodiments, the subject hashypertension. In some embodiments, the subject has hypertension withleft ventricular hypertrophy. In some embodiments, the subject hasdiabetes. In some embodiments, the subject has diabetes withhyperlipidemia. In some embodiments, the subject has an elevated levelof Galectin-3 in the blood or urine. In some embodiments, the subjecthas an elevated level of one or more fibrotic markers. In someembodiments, at least one of the one or more fibrotic markers is inblood. In some embodiments, at least one of the one or more fibroticmarkers is in urine. In some embodiments, the subject has an elevatedlevel of one or more markers of oxidative stress. In some embodiments,at least one of the markers of oxidative stress is in blood. In someembodiments, at least one of the markers of oxidative stress is inurine. In some embodiments, the subject has an elevated level of one ormore markers of inflammation. In some embodiments, at least one of theelevated markers is in urine. In some embodiments, the subject has heartfailure.

In some embodiments, a method of preventing heart failure in a subjectin need is provided. In some embodiments, the method comprisesidentifying a subject in need of prevention of heart failure andadministering the pharmaceutical formulation of any one of theembodiments described herein to a subject in need. In some embodiments,the pharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin and a pharmaceutical vehicle. In some embodiments,the pharmaceutical formulation further comprises a first lipid. In someembodiments, the first lipid is a phospholipid. In some embodiments, thefirst lipid is polyenylphosphatidylcholine. In some embodiments, thepharmaceutical formulation comprises at least 5% of the first lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the first lipid by weight. In some embodiments, thepharmaceutical formulation further comprises a second lipid. In someembodiments, the pharmaceutical formulation comprises at least 5% of thesecond lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the second lipid by weight. Insome embodiments, the second lipid is omega-3. In some embodiments, thesecond lipid is omega-3 from fish or flaxseed. In some embodiments, thepharmaceutical formulation further comprises an antioxidant. In someembodiments, the pharmaceutical formulation comprises at least 5% ofantioxidant by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the antioxidant by weight. Insome embodiments, the antioxidant is Vitamin E. In some embodiments, theantioxidant is Vitamin C. In some embodiments, the antioxidant is alphalipoic acid. In some embodiments, the pharmaceutical formulation furthercomprises curcumin. In some embodiments, the pharmaceutical formulationfurther comprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thevehicle is a lipophilic solvent, fatty oil, organic oil, or liposome. Insome embodiments, the pharmaceutical formulation further comprises anexcipient. In some embodiments, the excipient is a sugar, lactose,sucrose, mannitol, sorbitol, cellulose preparations of maize starch,wheat starch, rice starch, potato starch, gelatin, gum tragacanth,methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In someembodiments, the pharmaceutical formulation further comprises baicalin.In some embodiments, the subject has chronic kidney disease and/orhypertension. In some embodiments, the subject is human. In someembodiments, the administering is performed by oral administration. Insome embodiments, the administering is performed by intravenousadministration.

In some embodiments, a deuterated form of tetrahydrocurcumin isprovided. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least one deuterated site. In some embodiments, the deuteratedform of tetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons.

In some embodiments, a deuterated form of tetrahydrocurcumin isprovided. In some embodiments, the deuterated form of tetrahydrocurcuminis manufactured by any of the embodiments described herein. In someembodiments, a method of making a deuterated form of tetrahydrocurcuminis provided. In some embodiments, the method comprises contactingtetrahydrocurcumin in the presence of a catalyst and deuterated waterunder a condition to form the deuterated form of tetrahydrocurcumin. Insome embodiments, the method further comprises hydrogenating curcumin toform the tetrahydrocurcumin. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thanfifteen deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thantwenty-four deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons. In someembodiments, the catalyst is palladium on carbon. In some embodiments,the catalyst is palladium barium carbonate. In some embodiments, thecatalyst is palladium barium sulphate. In some embodiments, the catalystis palladium silica. In some embodiments, the catalyst is palladiumalumina. In some embodiments, the catalyst is platinum on carbon. Insome embodiments, the catalyst is platinum-palladium carbon. In someembodiments, the catalyst is platinum alumina. In some embodiments, thecatalyst is platinum calcium carbonate. In some embodiments, thecatalyst is platinum barium sulfate. In some embodiments, the catalystis platinum silica. In some embodiments, the catalyst is platinumgraphite. In some embodiments, the method further comprises purifyingthe deuterated form of tetrahydrocurcumin. In some embodiments, thepurifying step comprises isolating the deuterated form oftetrahydrocurcumin with column chromatography. In some embodiments, thedeuterated water is at least 25% deuterated. In some embodiments, thedeuterated water is at least 50% deuterated. In some embodiments, thedeuterated water is at least 75% deuterated. In some embodiments, thedeuterated water is 100% deuterated.

In some embodiments, a pharmaceutical formulation is provided. In someembodiments, the pharmaceutical formulation comprises thetetrahydrocurcumin of any of the embodiments described herein and apharmaceutical vehicle. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thanfifteen deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin is manufactured by any of the embodiments describedherein. In some embodiments, the method comprises contactingtetrahydrocurcumin in the presence of a catalyst and deuterated waterunder a condition to form the deuterated form of tetrahydrocurcumin. Insome embodiments, the method further comprises hydrogenating curcumin toform the tetrahydrocurcumin. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thanfifteen deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thantwenty-four deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons. In someembodiments, the catalyst is palladium on carbon. In some embodiments,the catalyst is palladium barium carbonate. In some embodiments, thecatalyst is palladium barium sulphate. In some embodiments, the catalystis palladium silica. In some embodiments, the catalyst is palladiumalumina. In some embodiments, the catalyst is platinum on carbon. Insome embodiments, the catalyst is platinum-palladium carbon. In someembodiments, the catalyst is platinum alumina. In some embodiments, thecatalyst is platinum calcium carbonate. In some embodiments, thecatalyst is platinum barium sulfate. In some embodiments, the catalystis platinum silica. In some embodiments, the catalyst is platinumgraphite. In some embodiments, the method further comprises purifyingthe deuterated form of tetrahydrocurcumin. In some embodiments, thepurifying step comprises isolating the deuterated form oftetrahydrocurcumin with column chromatography. In some embodiments, thedeuterated water is at least 25% deuterated. In some embodiments, thedeuterated water is at least 50% deuterated. In some embodiments, thedeuterated water is at least 75% deuterated. In some embodiments, thedeuterated water is 100% deuterated. In some embodiments, thepharmaceutical formulation further comprises a first lipid. In someembodiments, the first lipid is a phospholipid. In some embodiments, thefirst lipid is polyenylphosphatidylcholine. In some embodiments, thepharmaceutical formulation comprises at least 5% of the first lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the first lipid by weight. In some embodiments, thepharmaceutical formulation further comprises a second lipid. In someembodiments, the pharmaceutical formulation comprises at least 5% of thesecond lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the second lipid by weight. Insome embodiments, the second lipid is omega-3. In some embodiments, thesecond lipid is omega-3 from fish or flaxseed. In some embodiments, thepharmaceutical formulation further comprises an antioxidant. In someembodiments, the pharmaceutical formulation comprises at least 5% ofantioxidant by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the antioxidant by weight. Insome embodiments, the antioxidant is Vitamin E. In some embodiments, theantioxidant is Vitamin C. In some embodiments, the antioxidant is alphalipoic acid. In some embodiments, the pharmaceutical formulation furthercomprises curcumin. In some embodiments, the pharmaceutical formulationfurther comprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thepharmaceutical formulation further comprises baicalin. In someembodiments, the vehicle is a lipophilic solvent, fatty oil, organicoil, or liposome. In some embodiments, the pharmaceutical formulationfurther comprises an excipient. In some embodiments, the excipient is asugar, lactose, sucrose, mannitol, sorbitol, cellulose preparations ofmaize starch, wheat starch, rice starch, potato starch, gelatin, gumtragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP).

In some embodiments, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the methodcomprises administering the pharmaceutical formulation of any one of theembodiments described herein to the subject. In some embodiments, thepharmaceutical formulation comprises the tetrahydrocurcumin of any ofthe embodiments described herein and a pharmaceutical vehicle. In someembodiments, the deuterated form of tetrahydrocurcumin has at least onedeuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin is manufacturedby any of the embodiments described herein. In some embodiments, themethod comprises contacting tetrahydrocurcumin in the presence of acatalyst and deuterated water under a condition to form the deuteratedform of tetrahydrocurcumin. In some embodiments, the method furthercomprises hydrogenating curcumin to form the tetrahydrocurcumin. In someembodiments, the deuterated form of tetrahydrocurcumin has at least onedeuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than twenty-four deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons. In some embodiments, the catalyst is palladium on carbon. Insome embodiments, the catalyst is palladium barium carbonate. In someembodiments, the catalyst is palladium barium sulphate. In someembodiments, the catalyst is palladium silica. In some embodiments, thecatalyst is palladium alumina. In some embodiments, the catalyst isplatinum on carbon. In some embodiments, the catalyst isplatinum-palladium carbon. In some embodiments, the catalyst is platinumalumina. In some embodiments, the catalyst is platinum calciumcarbonate. In some embodiments, the catalyst is platinum barium sulfate.In some embodiments, the catalyst is platinum silica. In someembodiments, the catalyst is platinum graphite. In some embodiments, themethod further comprises purifying the deuterated form oftetrahydrocurcumin. In some embodiments, the purifying step comprisesisolating the deuterated form of tetrahydrocurcumin with columnchromatography. In some embodiments, the deuterated water is at least25% deuterated. In some embodiments, the deuterated water is at least50% deuterated. In some embodiments, the deuterated water is at least75% deuterated. In some embodiments, the deuterated water is 100%deuterated. In some embodiments, the pharmaceutical formulation furthercomprises a first lipid. In some embodiments, the first lipid is aphospholipid. In some embodiments, the first lipid ispolyenylphosphatidylcholine. In some embodiments, the pharmaceuticalformulation comprises at least 5% of the first lipid by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the first lipid by weight. In some embodiments, the pharmaceuticalformulation further comprises a second lipid. In some embodiments, thepharmaceutical formulation comprises at least 5% of the second lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the second lipid by weight. In some embodiments, thesecond lipid is omega-3. In some embodiments, the second lipid isomega-3 from fish or flaxseed. In some embodiments, the pharmaceuticalformulation further comprises an antioxidant. In some embodiments, thepharmaceutical formulation comprises at least 5% of antioxidant byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the antioxidant by weight. In some embodiments, theantioxidant is Vitamin E. In some embodiments, the antioxidant isVitamin C. In some embodiments, the antioxidant is alpha lipoic acid. Insome embodiments, the pharmaceutical formulation further comprisescurcumin. In some embodiments, the pharmaceutical formulation furthercomprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thepharmaceutical formulation further comprises baicalin. In someembodiments, the vehicle is a lipophilic solvent, fatty oil, organicoil, or liposome. In some embodiments, the pharmaceutical formulationfurther comprises an excipient. In some embodiments, the excipient is asugar, lactose, sucrose, mannitol, sorbitol, cellulose preparations ofmaize starch, wheat starch, rice starch, potato starch, gelatin, gumtragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In someembodiments, the disorder is a liver disorder. In some embodiments, thedisorder is a fatty liver disease. In some embodiments, the disorder isalcoholic liver disease. In some embodiments, the disorder is heartfailure. In some embodiments, the disorder is a kidney disease. In someembodiments, the disorder is diabetic kidney disease. In someembodiments, the disorder is polycystic kidney disease. In someembodiments, the disorder is hypertension. In some embodiments, thedisorder is hypertension with left ventricular hypertrophy. In someembodiments, the disorder is diabetes. In some embodiments, the disorderis diabetes with hyperlipidemia. In some embodiments, the subject haselevated Galectin-3 levels in the blood or urine. In some embodiments,the subject has elevated levels of fibrotic markers. In someembodiments, the fibrotic markers are in blood. In some embodiments, thefibrotic markers are in urine. In some embodiments, the subject has anelevated level of a marker of oxidative stress. In some embodiments, themarker of oxidative stress is in blood. In some embodiments, the markerof oxidative stress is in urine. In some embodiments, the subject has anelevated level of a marker of inflammation. In some embodiments, themarker of inflammation is in blood. In some embodiments, the marker ofinflammation is in urine. In some embodiments, the pharmaceuticalformulation is administered to the subject by oral administration. Insome embodiments, the administering is performed by intravenousadministration. In some embodiments, the subject is human. In someembodiments, the subject is taking analgesics. In some embodiments, thesubject is under treatment with one or more anti-malarial drugs.

In some embodiments, a method of protecting an organ is provided. Insome embodiments, the method comprises identifying a subject in need ofprotection of an organ and administering the pharmaceutical formulationof any one of the embodiments described herein, to a subject in need. Insome embodiments, the pharmaceutical formulation comprises thetetrahydrocurcumin of any of the embodiments described herein and apharmaceutical vehicle. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thanfifteen deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin is manufactured by any of the embodiments describedherein. In some embodiments, the method comprises contactingtetrahydrocurcumin in the presence of a catalyst and deuterated waterunder a condition to form the deuterated form of tetrahydrocurcumin. Insome embodiments, the method further comprises hydrogenating curcumin toform the tetrahydrocurcumin. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thanfifteen deuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin is deuterated at one or two alcohol sites. In someembodiments, the deuterated form of tetrahydrocurcumin has no more thantwenty-four deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons. In someembodiments, the catalyst is palladium on carbon. In some embodiments,the catalyst is palladium barium carbonate. In some embodiments, thecatalyst is palladium barium sulphate. In some embodiments, the catalystis palladium silica. In some embodiments, the catalyst is palladiumalumina. In some embodiments, the catalyst is platinum on carbon. Insome embodiments, the catalyst is platinum-palladium carbon. In someembodiments, the catalyst is platinum alumina. In some embodiments, thecatalyst is platinum calcium carbonate. In some embodiments, thecatalyst is platinum barium sulfate. In some embodiments, the catalystis platinum silica. In some embodiments, the catalyst is platinumgraphite. In some embodiments, the method further comprises purifyingthe deuterated form of tetrahydrocurcumin. In some embodiments, thepurifying step comprises isolating the deuterated form oftetrahydrocurcumin with column chromatography. In some embodiments, thedeuterated water is at least 25% deuterated. In some embodiments, thedeuterated water is at least 50% deuterated. In some embodiments, thedeuterated water is at least 75% deuterated. In some embodiments, thedeuterated water is 100% deuterated. In some embodiments, thepharmaceutical formulation further comprises a first lipid. In someembodiments, the first lipid is a phospholipid. In some embodiments, thefirst lipid is polyenylphosphatidylcholine. In some embodiments, thepharmaceutical formulation comprises at least 5% of the first lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the first lipid by weight. In some embodiments, thepharmaceutical formulation further comprises a second lipid. In someembodiments, the pharmaceutical formulation comprises at least 5% of thesecond lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the second lipid by weight. Insome embodiments, the second lipid is omega-3. In some embodiments, thesecond lipid is omega-3 from fish or flaxseed. In some embodiments, thepharmaceutical formulation further comprises an antioxidant. In someembodiments, the pharmaceutical formulation comprises at least 5% ofantioxidant by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the antioxidant by weight. Insome embodiments, the antioxidant is Vitamin E. In some embodiments, theantioxidant is Vitamin C. In some embodiments, the antioxidant is alphalipoic acid. In some embodiments, the pharmaceutical formulation furthercomprises curcumin. In some embodiments, the pharmaceutical formulationfurther comprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thepharmaceutical formulation further comprises baicalin. In someembodiments, the vehicle is a lipophilic solvent, fatty oil, organicoil, or liposome. In some embodiments, the pharmaceutical formulationfurther comprises an excipient. In some embodiments, the excipient is asugar, lactose, sucrose, mannitol, sorbitol, cellulose preparations ofmaize starch, wheat starch, rice starch, potato starch, gelatin, gumtragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In someembodiments, the organ is kidney. In some embodiments, the organ isliver. In some embodiments, the organ is heart. In some embodiments, thesubject is human. In some embodiments, the administering is performed byoral administration. In some embodiments, the administering is performedby intravenous administration. In some embodiments, the subject ishuman. In some embodiments, the subject has a liver disorder. In someembodiments, the subject has a fatty liver disease. In some embodiments,the subject has alcoholic liver disease. In some embodiments, thesubject has a kidney disease. In some embodiments, the subject hasdiabetic kidney disease. In some embodiments, the subject has polycystickidney disease. In some embodiments, the subject has hypertension. Insome embodiments, the subject has hypertension with left ventricularhypertrophy. In some embodiments, the subject has diabetes. In someembodiments, the subject has diabetes with hyperlipidemia. In someembodiments, the subject has an elevated level of Galectin-3 in theblood or urine. In some embodiments, the subject has an elevated levelof one or more fibrotic markers. In some embodiments, at least one ofthe one or more fibrotic markers is in blood. In some embodiments, atleast one of the one or more fibrotic markers is in urine. In someembodiments, the subject has an elevated level of one or more markers ofoxidative stress. In some embodiments, at least one of the markers ofoxidative stress is in blood. In some embodiments, at least one of themarkers of oxidative stress is in urine. In some embodiments, at leastone of the elevated markers of inflammation is in blood. In someembodiments, the subject has an elevated level of one or more markers ofinflammation. In some embodiments, at least one of the elevated markersof inflammation is in blood. In some embodiments, at least one of theelevated markers is in urine. In some embodiments, the subject has heartfailure.

In some embodiments, a method of treating or preventing heart failure ina subject in need is provided. In some embodiments, the method comprisesidentifying a subject in need of treatment for or prevention of heartfailure and administering the pharmaceutical formulation of any of theembodiments described herein to a subject in need. In some embodiments,the pharmaceutical formulation comprises the tetrahydrocurcumin of anyof the embodiments described herein and a pharmaceutical vehicle. Insome embodiments, the deuterated form of tetrahydrocurcumin has at leastone deuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin is manufacturedby any of the embodiments described herein. In some embodiments, themethod comprises contacting tetrahydrocurcumin in the presence of acatalyst and deuterated water under a condition to form the deuteratedform of tetrahydrocurcumin. In some embodiments, the method furthercomprises hydrogenating curcumin to form the tetrahydrocurcumin. In someembodiments, the deuterated form of tetrahydrocurcumin has at least onedeuterated site. In some embodiments, the deuterated form oftetrahydrocurcumin has at least five deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least tendeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than fifteen deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has no more than twenty-four deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 1deuteron. In some embodiments, the deuterated form of tetrahydrocurcuminhas at least 5 deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 10 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 20 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 24deuterons. In some embodiments, the catalyst is palladium on carbon. Insome embodiments, the catalyst is palladium barium carbonate. In someembodiments, the catalyst is palladium barium sulphate. In someembodiments, the catalyst is palladium silica. In some embodiments, thecatalyst is palladium alumina. In some embodiments, the catalyst isplatinum on carbon. In some embodiments, the catalyst isplatinum-palladium carbon. In some embodiments, the catalyst is platinumalumina. In some embodiments, the catalyst is platinum calciumcarbonate. In some embodiments, the catalyst is platinum barium sulfate.In some embodiments, the catalyst is platinum silica. In someembodiments, the catalyst is platinum graphite. In some embodiments, themethod further comprises purifying the deuterated form oftetrahydrocurcumin. In some embodiments, the purifying step comprisesisolating the deuterated form of tetrahydrocurcumin with columnchromatography. In some embodiments, the deuterated water is at least25% deuterated. In some embodiments, the deuterated water is at least50% deuterated. In some embodiments, the deuterated water is at least75% deuterated. In some embodiments, the deuterated water is 100%deuterated. In some embodiments, the pharmaceutical formulation furthercomprises a first lipid. In some embodiments, the first lipid is aphospholipid. In some embodiments, the first lipid ispolyenylphosphatidylcholine. In some embodiments, the pharmaceuticalformulation comprises at least 5% of the first lipid by weight. In someembodiments, the pharmaceutical formulation comprises no more than 95%of the first lipid by weight. In some embodiments, the pharmaceuticalformulation further comprises a second lipid. In some embodiments, thepharmaceutical formulation comprises at least 5% of the second lipid byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the second lipid by weight. In some embodiments, thesecond lipid is omega-3. In some embodiments, the second lipid isomega-3 from fish or flaxseed. In some embodiments, the pharmaceuticalformulation further comprises an antioxidant. In some embodiments, thepharmaceutical formulation comprises at least 5% of antioxidant byweight. In some embodiments, the pharmaceutical formulation comprises nomore than 95% of the antioxidant by weight. In some embodiments, theantioxidant is Vitamin E. In some embodiments, the antioxidant isVitamin C. In some embodiments, the antioxidant is alpha lipoic acid. Insome embodiments, the pharmaceutical formulation further comprisescurcumin. In some embodiments, the pharmaceutical formulation furthercomprises a terpenoid. In some embodiments, the pharmaceuticalformulation further comprises cysteamine. In some embodiments, thepharmaceutical formulation further comprises pantethine. In someembodiments, the curcumin is deuterated. In some embodiments, thepharmaceutical formulation further comprises baicalin. In someembodiments, the vehicle is a lipophilic solvent, fatty oil, organicoil, or liposome. In some embodiments, the pharmaceutical formulationfurther comprises an excipient. In some embodiments, the excipient is asugar, lactose, sucrose, mannitol, sorbitol, cellulose preparations ofmaize starch, wheat starch, rice starch, potato starch, gelatin, gumtragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodiumcarboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). In someembodiments, the subject has chronic kidney disease and/or hypertension.In some embodiments, the subject is human. In some embodiments, theadministering is performed by oral administration. In some embodiments,the administering is performed by intravenous administration.

In one aspect a method of manufacturing tetrahydrocurcumin from curcuminis contemplated. In some embodiments, the tetrahydrocurcumin isdeuterated.

In another aspect, tetrahydrocurcumin is manufactured synthetically. Insome embodiments, curcumin is not a substrate in the manufacturing oftetrahydrocurcumin. In some embodiments, the tetrahydrocurcumin isdeuterated.

In some embodiments, a pharmaceutical formulation, for example apharmaceutical formulation, comprising a non-deuterated form oftetrahydrocurcumin is provided. In some embodiments, the pharmaceuticalformulation further comprises a pharmaceutical vehicle. In someembodiments, the pharmaceutical formulation can further comprise adeuterated form of tetrahydrocurcumin and a pharmaceutical vehicle. Insome embodiments, the deuterated form of tetrahydrocurcumin has no morethan fifteen deuterated sites. In some embodiments, the deuterated formof tetrahydrocurcumin has at least ten deuterated sites. In someembodiments, the deuterated form of tetrahydrocurcumin has at least fivedeuterated sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least one deuterated site. In someembodiments, the deuterated form of tetrahydrocurcumin is deuterated atone or two alcohol sites. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 1 deuteron. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 5 deuterons. In someembodiments, the deuterated form of tetrahydrocurcumin has at least 10deuterons. In some embodiments, the deuterated form oftetrahydrocurcumin has at least 20 deuterons. In some embodiments, thedeuterated form of tetrahydrocurcumin has at least 24 deuterons.

In some embodiments, the pharmaceutical formulation further comprises afirst lipid. In some embodiments, the first lipid is a phospholipid. Insome embodiments, the first lipid is polyenylphosphatidylcholine. Insome embodiments, the pharmaceutical formulation comprises at least 5%of the first lipid by weight. In some embodiments, the pharmaceuticalformulation comprises no more than 95% of the first lipid by weight. Insome embodiments, the pharmaceutical formulation comprises a secondlipid. In some embodiments, the pharmaceutical formulation comprises atleast 5% of the second lipid by weight. In some embodiments, thepharmaceutical formulation comprises no more than 95% of the secondlipid by weight. In some embodiments, the second lipid is omega-3. Insome embodiments, the second lipid is omega-3 from fish or flaxseed.

In some embodiments, the pharmaceutical formulation comprises anantioxidant. In some embodiments, the pharmaceutical formulationcomprises at least 5% of antioxidant by weight. In some embodiments, thepharmaceutical formulation comprises no more than 95% of the antioxidantby weight. In some embodiments, the antioxidant is Vitamin E. In someembodiments, the antioxidant is Vitamin C. In some embodiments, theantioxidant is alpha lipoic acid.

In some embodiments, the pharmaceutical formulation further comprisescurcumin. In some embodiments, the curcumin is deuterated. In someembodiments, the pharmaceutical formulation comprises a terpenoid. Insome embodiments, the pharmaceutical formulation comprises cysteamine.In some embodiments, the pharmaceutical formulation comprisespantethine. In some embodiments, the pharmaceutical formulationcomprises baicalin.

In some embodiments, a method of treating, inhibiting, or ameliorating adisorder in a subject is provided. In some embodiments, the methodcomprises administering a pharmaceutical formulation according to any ofthe embodiments described herein to the subject. In some embodiments,the pharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin. In some embodiments, the pharmaceutical formulationcomprises a deuterated form of tetrahydrocurcumin. In some embodiments,the pharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin and a deuterated form of tetrahydrocurcumin. In someembodiments, the disorder is a liver disorder. In some embodiments, thedisorder is a fatty liver disease. In some embodiments, the disorder isalcoholic liver disease. In some embodiments, the disorder is a kidneydisease. In some embodiments, the disorder is diabetic kidney disease.In some embodiments, the disorder is polycystic kidney disease. In someembodiments, the disorder is heart failure.

In some embodiments, the pharmaceutical formulation is administered totreat, prevent or ameliorate a disease. In some embodiments, the diseaseis hypertension or cardiac hypertrophy.

In some embodiments, the pharmaceutical formulation is administered totreat a subject suffering from heart failure. In some embodiments, thepharmaceutical formulation is administered to a subject to prevent heartfailure. In some embodiments, the subject suffers from hypertension. Insome embodiments, the subject suffers from chronic kidney disease.

In some embodiments, the disorder is hypertension. In some embodiments,the disorder is hypertension with left ventricular hypertrophy. In someembodiments, the disorder is diabetes. In some embodiments, the disorderis diabetes with hyperlipidemia. In some embodiments, the disorder iscardiac hypertrophy.

In some embodiments, the subject has elevated Galectin-3 levels in theblood. In some embodiments, the subject has elevated levels of fibroticmarkers. In some embodiments, the fibrotic markers are in blood. In someembodiments, the fibrotic markers are in urine. In some embodiments, thesubject has an elevated level of a marker of oxidative stress. In someembodiments, the marker of oxidative stress is in blood. In someembodiments, the marker of oxidative stress is in urine. In someembodiments, the subject has an elevated level of a marker ofinflammation. In some embodiments, the marker of inflammation is inblood. In some embodiments, the marker of inflammation is in urine.

In some embodiments, the pharmaceutical formulation is administered tothe subject by oral administration. In some embodiments, thepharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin. In some embodiments, the pharmaceutical formulationcomprises a deuterated form of tetrahydrocurcumin. In some embodiments,the pharmaceutical formulation comprises a non-deuterated form oftetrahydrocurcumin and a deuterated form of tetrahydrocurcumin. In someembodiments, the subject is human. In some embodiments, theadministering is performed by intravenous administration. In someembodiments, the subject is under treatment with one or moreanti-malarial drugs.

In some embodiments, a method of protecting an organ is provided. Insome embodiments, the method comprises identifying a subject in need ofprotection of an organ and administering the pharmaceutical formulationaccording to any of the embodiments described herein to the subject inneed. In some embodiments, the pharmaceutical formulation comprises anon-deuterated form of tetrahydrocurcumin. In some embodiments, thepharmaceutical formulation comprises a deuterated form oftetrahydrocurcumin. In some embodiments, the pharmaceutical formulationcomprises a non-deuterated form of tetrahydrocurcumin and a deuteratedform of tetrahydrocurcumin. In some embodiments, the organ is kidney. Insome embodiments, the organ is liver. In some embodiments, the subjectis human. In some embodiments, the organ is heart.

In some embodiments, the administering is performed by oraladministration. In some embodiments, the administering is performed byintravenous administration. In some embodiments, the subject has a liverdisorder. In some embodiments, the subject has a fatty liver disease. Insome embodiments, the subject has alcoholic liver disease. In someembodiments, the subject has a kidney disease. In some embodiments, thesubject has diabetic kidney disease. In some embodiments, the subjecthas polycystic kidney disease. In some embodiments, the subject hasheart failure.

In some embodiments, the subject has hypertension. In some embodiments,the subject has hypertension with left ventricular hypertrophy. In someembodiments, the subject has diabetes. In some embodiments, the subjecthas diabetes with hyperlipidemia.

In some embodiments, the subject has an elevated level of Galectin-3 inthe blood. In some embodiments, the subject has an elevated level of oneor more fibrotic markers. In some embodiments, the one or more fibroticmarkers are in blood. In some embodiments, at least one of the one ormore fibrotic markers is in urine. In some embodiments, the subject hasan elevated level of one or more markers of oxidative stress. In someembodiments, at least one of the markers of oxidative stress is inblood. In some embodiments, at least one of the markers of oxidativestress is in urine. In some embodiments, the subject has an elevatedlevel of one or more markers of inflammation. In some embodiments, atleast one of the elevated markers of inflammation is in blood. In someembodiments, at least one of the elevated markers is in urine.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should be interpreted to mean “at least one”or “one or more”); the same holds true for the use of definite articlesused to introduce claim recitations. In addition, even if a specificnumber of an introduced claim recitation is explicitly recited, thoseskilled in the art will recognize that such recitation should beinterpreted to mean at least the recited number (e.g., the barerecitation of “two recitations,” without other modifiers, means at leasttwo recitations, or two or more recitations). Furthermore, in thoseinstances where a convention analogous to “at least one of A, B, and C,etc.” is used, in general such a construction is intended in the senseone having skill in the art would understand the convention (e.g., “ asystem having at least one of A, B, and C” would include but not belimited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, and/or A, B, and Ctogether, etc.). In those instances where a convention analogous to “atleast one of A, B, or C, etc.” is used, in general such a constructionis intended in the sense one having skill in the art would understandthe convention (e.g., “ a system having at least one of A, B, or C”would include but not be limited to systems that have A alone, B alone,C alone, A and B together, A and C together, B and C together, and/or A,B, and C together, etc.). It will be further understood by those withinthe art that virtually any disjunctive word and/or phrase presenting twoor more alternative terms, whether in the description, claims, ordrawings, should be understood to contemplate the possibilities ofincluding one of the terms, either of the terms, or both terms. Forexample, the phrase “A or B” will be understood to include thepossibilities of “A” or “B” or “A and B.”

In addition, where features or aspects of the disclosure are describedin terms of Markush groups, those skilled in the art will recognize thatthe disclosure is also thereby described in terms of any individualmember or subgroup of members of the Markush group.

What is claimed is:
 1. A method of treating, inhibiting, or amelioratinga disorder in a subject comprising: administering a pharmaceuticalformulation to the subject, the pharmaceutical formulation comprising anon-deuterated form of tetrahydrocurcumin or a deuterated form oftetrahydrocurcumin and a pharmaceutical vehicle.
 2. The method of claim1, wherein the disorder is selected from a group consisting ofconsisting of fatty liver disease, alcoholic liver disease, kidneydisease, diabetic kidney disease, polycystic kidney disease,hypertension, hypertension with left ventricular hypertrophy, heartfailure, diabetes and diabetes with hyperlipidemia.
 3. The method ofclaim 1, wherein the disorder is chronic kidney disease.
 4. The methodof claim 1, wherein the subject has elevated levels of Galectin-3,fibrotic markers, markers of oxidative stress, and/or markers ofinflammation in the blood and/or urine, or , wherein the subject istaking analgesics, or wherein the subject is under treatment with one ormore anti-malarial drugs.
 5. The method of claim 1, wherein thepharmaceutical formulation is administered by oral administration orintravenous administration.
 6. A method of protecting an organ,comprising: identifying a subject in need of protection of an organ; andadministering a pharmaceutical formulation to a subject in need thereof,the pharmaceutical formulation comprising a non-deuterated form oftetrahydrocurcumin or a deuterated form of tetrahydrocurcumin and apharmaceutical vehicle.
 7. The method of claim 6, wherein the organ isselected from a group consisting of kidney, liver and heart.
 8. Themethod of claim 6, wherein the administering is performed by oraladministration or intravenous administration.
 9. The method of claim 6,wherein the subject has a disorder selected from a group consistingliver disorder, fatty liver disease, alcoholic liver disease, kidneydisease, chronic kidney disease, diabetic kidney disease, polycystickidney disease, hypertension, hypertension with left ventricularhypertrophy, diabetes, diabetes with hyperlipidemia and heart failure.10. The method of claim 5, wherein the subject has an elevated level ofGalectin-3, fibrotic markers, markers of oxidative stress and/or one ormore markers of inflammation in the blood and/or urine.
 11. A method oftreating or preventing heart failure in a subject in need, comprising:identifying a subject in need of treatment for or prevention of heartfailure; and administering pharmaceutical formulation to a subject inneed thereof, the pharmaceutical formulation comprising a non-deuteratedform of tetrahydrocurcumin or a deuterated form of tetrahydrocurcuminand a pharmaceutical vehicle.
 12. The method of claim 10, wherein thesubject has chronic kidney disease and/or hypertension.
 13. The methodof claim 10, wherein the administering is oral administration orintravenous administration.
 14. A pharmaceutical formulation comprisinga non-deuterated form of tetrahydrocurcumin or a deuterated form oftetrahydrocurcumin and a pharmaceutical vehicle.
 15. The pharmaceuticalformulation of claim 13, further comprising a first lipid, wherein thefirst lipid is a phospholipid or polyenylphosphatidylcholine, andwherein the pharmaceutical formulation comprises at least 5% of thefirst lipid by weight and no more than 95% of the first lipid by weight.16. The pharmaceutical formulation of claim 14, further comprising asecond lipid, and wherein the pharmaceutical formulation comprises atleast 5% of the second lipid by weight and no more than 95% of thesecond lipid by weight.
 17. The pharmaceutical formulation of claim 13,wherein the pharmaceutical formulation further comprises an antioxidant,and wherein the pharmaceutical formulation comprises at least 5% ofantioxidant by weight and no more than 95% of the antioxidant by weight,and wherein the antioxidant is selected from a group consisting ofVitamin E, Vitamin C and alpha lipoic acid.
 18. The pharmaceuticalformulation of claim 13, wherein the pharmaceutical formulation furthercomprises curcumin, a terpenoid, cysteamine, pantethine, and/orbaicalin.
 19. The pharmaceutical formulation of claim 13, wherein thevehicle is a lipophilic solvent, fatty oil, organic oil, or liposome.20. The pharmaceutical formulation of claim 13, wherein thepharmaceutical formulation further comprises an excipient, wherein theexcipient is a sugar, lactose, sucrose, mannitol, sorbitol, cellulosepreparations of maize starch, wheat starch, rice starch, potato starch,gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP).